CAR-T Cell Therapy - Revision history

MesotheliomaSupport: Sprint 3c citation-remediation batch deploy (RON #9219)

2026-05-25T05:04:53Z

Sprint 3c citation-remediation batch deploy (RON #9219)

← Older revision		Revision as of 05:04, 25 May 2026
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	~~Connecting to wikimesothelioma.com...~~
	~~Logging in as MesotheliomaSupport@Claude...~~
	~~Successfully logged in!~~

	~~--- Page Content ---~~
	{{#seo:		{{#seo:
	\|title=CAR-T Cell Therapy for Mesothelioma: Clinical Trials, Targets & Outcomes		\|title=CAR-T Cell Therapy for Mesothelioma: Clinical Trials, Targets & Outcomes
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	\|author=WikiMesothelioma Medical Editorial Team		\|author=WikiMesothelioma Medical Editorial Team
	\|published_time=2026-03-03		\|published_time=2026-03-03
	~~\|type=Article~~		}}
	~~\|image=logo.png~~
	~~\|twitter_card=summary_large_image~~}}

	== CAR-T Cell Therapy for Mesothelioma ==		= CAR-T Cell Therapy for Mesothelioma =

	== Overview ==		== Overview ==
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	<ref name="biorxiv">[http://biorxiv.org/lookup/doi/10.1101/2024.09.27.615167 A balanced CAR-T cell metabolism driven by CD28 or 4-1BB co-stimulation], bioRxiv (2024)</ref>		<ref name="biorxiv">[http://biorxiv.org/lookup/doi/10.1101/2024.09.27.615167 A balanced CAR-T cell metabolism driven by CD28 or 4-1BB co-stimulation], bioRxiv (2024)</ref>
	<ref name="pmcpleural">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8184643/ CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials], PMC (2021)</ref>		<ref name="pmcpleural">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8184643/ CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials], PMC (2021)</ref>
	<ref name="pubmedhuCart">[https://pubmed.ncbi.nlm.nih.gov/41566776/ ~~Phase I study of autologous T cells bearing fully human chimeric antigen receptor targeting mesothelin~~]~~, PubMed (2025)~~</ref>		<ref name="pubmedhuCart">Barber-Rotenberg JS, Haas AR, Aggarwal C, et al. Phase 1 study of autologous T cells bearing fully human chimeric antigen receptors targeting mesothelin in mesothelin-expressing cancers. ''Mol Ther.'' 2026;34(5):2653-2665. PMID 41566776. [https://pubmed.ncbi.nlm.nih.gov/41566776/ PubMed]</ref>
	<ref name="pmcadvances">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8555868/ Malignant mesothelioma: Advances in immune checkpoint inhibitor and mesothelin-targeted therapies], PMC (2021)</ref>		<ref name="pmcadvances">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8555868/ Malignant mesothelioma: Advances in immune checkpoint inhibitor and mesothelin-targeted therapies], PMC (2021)</ref>
	<ref name="pmcmsln3">[https://pmc.ncbi.nlm.nih.gov/articles/PMC5477819/ Mesothelin Immunotherapy for Cancer: Ready for Prime Time?], PMC (2017)</ref>		<ref name="pmcmsln3">[https://pmc.ncbi.nlm.nih.gov/articles/PMC5477819/ Mesothelin Immunotherapy for Cancer: Ready for Prime Time?], PMC (2017)</ref>
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	<ref name="jnmfap2">[http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.125.270906 Prognostic Value of FAP-Directed PET Imaging in Pleural Mesothelioma], Journal of Nuclear Medicine (2025)</ref>		<ref name="jnmfap2">[http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.125.270906 Prognostic Value of FAP-Directed PET Imaging in Pleural Mesothelioma], Journal of Nuclear Medicine (2025)</ref>
	<ref name="elsevfap">[https://linkinghub.elsevier.com/retrieve/pii/S0923753419594388 Phase I clinical trial of malignant pleural mesothelioma treated with locally delivered anti-FAP CAR T-cells], Annals of Oncology (2019)</ref>		<ref name="elsevfap">[https://linkinghub.elsevier.com/retrieve/pii/S0923753419594388 Phase I clinical trial of malignant pleural mesothelioma treated with locally delivered anti-FAP CAR T-cells], Annals of Oncology (2019)</ref>
	<ref name="pubmedfap">~~[https://pubmed.ncbi~~.~~nlm.nih.gov/33098996/~~ Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma], ~~PubMed~~ (~~2020~~)</ref>		<ref name="pubmedfap">Hiltbrunner S, Britschgi C, Schuberth P, et al. Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma: first report of FAPME, a phase I clinical trial. ''Ann Oncol.'' 2020;32(1):120-121. PMID 33098996. [https://pubmed.ncbi.nlm.nih.gov/33098996/ PubMed]</ref>
	<ref name="pmcher2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC2862534/ Case Report of a Serious Adverse Event Following HER2 CAR-T Cell Administration], PMC (2010)</ref>		<ref name="pmcher2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC2862534/ Case Report of a Serious Adverse Event Following HER2 CAR-T Cell Administration], PMC (2010)</ref>
	<ref name="pmcher2low">[https://pmc.ncbi.nlm.nih.gov/articles/PMC11145640/ Systemically administered low-affinity HER2 CAR T cells mediate antitumor activity], PMC (2024)</ref>		<ref name="pmcher2low">[https://pmc.ncbi.nlm.nih.gov/articles/PMC11145640/ Systemically administered low-affinity HER2 CAR T cells mediate antitumor activity], PMC (2024)</ref>
	<ref name="pmcdual">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8570569/ Dual Targeting CAR-T Cells with Optimal Costimulation and Metabolic Fitness], PMC (2021)</ref>		<ref name="pmcdual">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8570569/ Dual Targeting CAR-T Cells with Optimal Costimulation and Metabolic Fitness], PMC (2021)</ref>
	<ref name="pmcmet">[https://pmc.ncbi.nlm.nih.gov/articles/PMC5706532/ CAR T-cell immunotherapy of MET-expressing malignant mesothelioma], PMC (2017)</ref>		<ref name="pmcmet">[https://pmc.ncbi.nlm.nih.gov/articles/PMC5706532/ CAR T-cell immunotherapy of MET-expressing malignant mesothelioma], PMC (2017)</ref>
	<ref name="pubmedmskcc">~~[https://pubmed~~.~~ncbi.nlm.nih.gov/34266984/~~ A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease], ~~PubMed~~ (~~2021~~)</ref>		<ref name="pubmedmskcc">Adusumilli PS, Zauderer MG, Rivière I, et al. A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab. ''Cancer Discov.'' 2021;11(11):2748-2763. PMID 34266984. [https://pubmed.ncbi.nlm.nih.gov/34266984/ PubMed]</ref>
	<ref name="pmcmskcc">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8563385/ Phase I trial of regional mesothelin-targeted CAR T-cell therapy with anti-PD-1 pembrolizumab], PMC (2021)</ref>		<ref name="pmcmskcc">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8563385/ Phase I trial of regional mesothelin-targeted CAR T-cell therapy with anti-PD-1 pembrolizumab], PMC (2021)</ref>
	<ref name="vbcancer">[https://www.valuebasedcancer.com/issues/2019/august-2019-vol-10-no-4/autologous-mesothelin-targeted-t-cells-induce-responses-in-pleural-solid-tumors Autologous Mesothelin-Targeted T-Cells Induce Responses in Pleural Solid Tumors], Value-Based Cancer Care (2019)</ref>		<ref name="vbcancer">[https://www.valuebasedcancer.com/issues/2019/august-2019-vol-10-no-4/autologous-mesothelin-targeted-t-cells-induce-responses-in-pleural-solid-tumors Autologous Mesothelin-Targeted T-Cells Induce Responses in Pleural Solid Tumors], Value-Based Cancer Care (2019)</ref>
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	<ref name="mesoatty">[https://mesotheliomaattorney.com/ Mesothelioma Attorney — Legal Compensation for Asbestos Exposure Victims], MesotheliomaAttorney.com</ref>		<ref name="mesoatty">[https://mesotheliomaattorney.com/ Mesothelioma Attorney — Legal Compensation for Asbestos Exposure Victims], MesotheliomaAttorney.com</ref>
	<ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>		<ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>
	<ref name="gavocel">[https://pubmed.ncbi.nlm.nih.gov/~~37474806~~/ ~~Gavocabtagene autoleucel (gavo-cel), an autologous anti-mesothelin TRuC-T cell therapy, in patients with mesothelin-expressing cancers: a phase 1 clinical trial~~]~~, Nature Medicine (2023)~~</ref>		<ref name="gavocel">Hassan R, Butler M, O'Cearbhaill RE, et al. Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results. ''Nat Med.'' 2023;29(8):2099-2109. PMID 37501016. [https://pubmed.ncbi.nlm.nih.gov/37501016/ PubMed]</ref>
	<ref name="nact">~~Sun Y, Yang H, Xu Q, Li X, Lou J, Duan J, et al.~~ [https://pubmed.ncbi.nlm.nih.gov/41134065/ Anti-PD-1 Nanobody-Armored MSLN CAR-T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies]. Advanced Science (~~Weinheim~~)~~. 2025;e08754. PMID: 41134065.~~</ref>		<ref name="nact">[https://pubmed.ncbi.nlm.nih.gov/41134065/ Anti-PD-1 Nanobody-Armored MSLN CAR-T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies], Advanced Science (2025)</ref>
	<ref name="pmcmsln95">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,448 Tumors], PMC (2021) — reports mesothelin overexpression in approximately 95% of epithelioid pleural mesotheliomas</ref>		<ref name="pmcmsln95">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,448 Tumors], PMC (2021) — reports mesothelin overexpression in approximately 95% of epithelioid pleural mesotheliomas</ref>
	</references>		</references>

MesotheliomaSupport: Fix 7b: demote body H1 to H2 (ALFRED audit #6922)

2026-05-14T23:06:50Z

Fix 7b: demote body H1 to H2 (ALFRED audit #6922)

← Older revision		Revision as of 23:06, 14 May 2026
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	\|twitter_card=summary_large_image}}		\|twitter_card=summary_large_image}}

	= CAR-T Cell Therapy for Mesothelioma =		== CAR-T Cell Therapy for Mesothelioma ==

	== Overview ==		== Overview ==

MesotheliomaSupport: Fix #6165 fab: replace fake PMID 39400460 with real NAC-T PMID 41134065 (Sun et al. Adv Sci 2025)

2026-05-12T12:35:57Z

Fix #6165 fab: replace fake PMID 39400460 with real NAC-T PMID 41134065 (Sun et al. Adv Sci 2025)

← Older revision		Revision as of 12:35, 12 May 2026
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			Connecting to wikimesothelioma.com...
			Logging in as MesotheliomaSupport@Claude...
			Successfully logged in!

			--- Page Content ---
	{{#seo:		{{#seo:
	\|title=CAR-T Cell Therapy for Mesothelioma: Clinical Trials, Targets & Outcomes		\|title=CAR-T Cell Therapy for Mesothelioma: Clinical Trials, Targets & Outcomes
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	<ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>		<ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>
	<ref name="gavocel">[https://pubmed.ncbi.nlm.nih.gov/37474806/ Gavocabtagene autoleucel (gavo-cel), an autologous anti-mesothelin TRuC-T cell therapy, in patients with mesothelin-expressing cancers: a phase 1 clinical trial], Nature Medicine (2023)</ref>		<ref name="gavocel">[https://pubmed.ncbi.nlm.nih.gov/37474806/ Gavocabtagene autoleucel (gavo-cel), an autologous anti-mesothelin TRuC-T cell therapy, in patients with mesothelin-expressing cancers: a phase 1 clinical trial], Nature Medicine (2023)</ref>
	<ref name="nact">[https://pubmed.ncbi.nlm.nih.gov/~~39400460~~/ Anti-PD-1 ~~nanobody~~-~~armored anti-mesothelin~~ CAR-T ~~cells (NAC-T)~~ for ~~malignant mesothelioma~~: ~~first-in-human results~~], Advanced Science (2025)</ref>		<ref name="nact">Sun Y, Yang H, Xu Q, Li X, Lou J, Duan J, et al. [https://pubmed.ncbi.nlm.nih.gov/41134065/ Anti-PD-1 Nanobody-Armored MSLN CAR-T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies]. Advanced Science (Weinheim). 2025;e08754. PMID: 41134065.</ref>
	<ref name="pmcmsln95">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,448 Tumors], PMC (2021) — reports mesothelin overexpression in approximately 95% of epithelioid pleural mesotheliomas</ref>		<ref name="pmcmsln95">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,448 Tumors], PMC (2021) — reports mesothelin overexpression in approximately 95% of epithelioid pleural mesotheliomas</ref>
	</references>		</references>

MesotheliomaSupport: RON: Add OG/Twitter meta — type=Article, image=logo.png, twitter_card=summary_large_image

2026-04-25T14:15:14Z

RON: Add OG/Twitter meta — type=Article, image=logo.png, twitter_card=summary_large_image

← Older revision		Revision as of 14:15, 25 April 2026
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	\|author=WikiMesothelioma Medical Editorial Team		\|author=WikiMesothelioma Medical Editorial Team
	\|published_time=2026-03-03		\|published_time=2026-03-03
	}}		\|type=Article
			\|image=logo.png
			\|twitter_card=summary_large_image}}

	= CAR-T Cell Therapy for Mesothelioma =		= CAR-T Cell Therapy for Mesothelioma =

MesotheliomaSupport: Fix MediaWiki cite errors: remove unused ref definitions / move references block to end

2026-04-22T16:36:19Z

Fix MediaWiki cite errors: remove unused ref definitions / move references block to end

← Older revision		Revision as of 16:36, 22 April 2026
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	<ref name="pmcmsln">[https://pmc.ncbi.nlm.nih.gov/articles/PMC10952516/ High mesothelin expression by immunohistochemistry predicts poor clinical outcomes], PMC (2024)</ref>		<ref name="pmcmsln">[https://pmc.ncbi.nlm.nih.gov/articles/PMC10952516/ High mesothelin expression by immunohistochemistry predicts poor clinical outcomes], PMC (2024)</ref>
	<ref name="pmcmsln2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study], PMC (2021)</ref>		<ref name="pmcmsln2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study], PMC (2021)</ref>
	<ref name="ascopost">[https://ascopost.com/issues/april-25-2019/preliminary-results-show-activity-for-mesothelin-directed-car-t-cell-therapy-in-malignant-mesothelioma/ Preliminary Results Show Activity for Mesothelin-Directed CAR T-Cell Therapy in Malignant Mesothelioma], The ASCO Post (2019)</ref>
	<ref name="ijpmmm">[https://journals.lww.com/10.4103/IJPMMM.IJPMMM_4_25 From concept to cure: CAR T-cell therapy molecular mechanisms, clinical triumphs, and future horizons], Indian Journal of Pathology and Microbiology (2025)</ref>		<ref name="ijpmmm">[https://journals.lww.com/10.4103/IJPMMM.IJPMMM_4_25 From concept to cure: CAR T-cell therapy molecular mechanisms, clinical triumphs, and future horizons], Indian Journal of Pathology and Microbiology (2025)</ref>
	<ref name="pmcfap">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/ Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells], PMC (2021)</ref>		<ref name="pmcfap">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/ Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells], PMC (2021)</ref>

MesotheliomaSupport: Add missing gavocel, nact, pmcmsln95 ref definitions

2026-04-19T11:23:28Z

Add missing gavocel, nact, pmcmsln95 ref definitions

MesotheliomaSupport: Fix reference errors (RON weekly sweep)

2026-04-19T11:20:12Z

Fix reference errors (RON weekly sweep)

MesotheliomaSupport: Corrected ORR data to verified PMID 34266984 — CLEO QA 91/100

2026-04-14T07:05:28Z

Corrected ORR data to verified PMID 34266984 — CLEO QA 91/100

← Older revision		Revision as of 07:05, 14 April 2026
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	=== CAR-T Plus Checkpoint Inhibitors ===		=== CAR-T Plus Checkpoint Inhibitors ===

	The combination of CAR-T cells with anti-PD-1 therapy (such as pembrolizumab) is the most extensively studied and most successful approach in mesothelioma. When CAR-T cells enter the tumor microenvironment, they can become "exhausted" through PD-1/PD-L1 signaling — essentially being switched off by the tumor. Adding pembrolizumab blocks this exhaustion pathway, rescuing the CAR-T cells and restoring their cancer-killing function. This combination strategy produced the ~~remarkable 72~~% ~~response rate in~~ the ~~MSKCC trial,~~ demonstrating that CAR-T and checkpoint inhibitors are synergistic ~~— working together far better than either approach alone~~.<ref name="~~ascopost~~" /><ref name="pmcmskcc~~" /><ref name="onclive1" /><ref name="mlc~~" />		The combination of CAR-T cells with anti-PD-1 therapy (such as pembrolizumab) is the most extensively studied and most successful approach in mesothelioma. When CAR-T cells enter the tumor microenvironment, they can become "exhausted" through PD-1/PD-L1 signaling — essentially being switched off by the tumor. Adding pembrolizumab blocks this exhaustion pathway, rescuing the CAR-T cells and restoring their cancer-killing function. This combination strategy produced the MSKCC trial's 23.9-month median OS and 83% 1-year survival — the most encouraging solid-tumor CAR-T results to date — demonstrating that CAR-T and checkpoint inhibitors are synergistic.<ref name="pubmedmskcc" /><ref name="pmcmskcc" />

	The next-generation MSKCC CAR (M28z1XXPD1DNR) incorporates a PD-1 dominant-negative receptor directly into the CAR construct, potentially achieving the same checkpoint-resistant effect without requiring concurrent antibody therapy — a design that could simplify treatment and reduce costs.<ref name="nctpd1dnr" /><ref name="onclive1" />		The next-generation MSKCC CAR (M28z1XXPD1DNR) incorporates a PD-1 dominant-negative receptor directly into the CAR construct, potentially achieving the same checkpoint-resistant effect without requiring concurrent antibody therapy — a design that could simplify treatment and reduce costs.<ref name="nctpd1dnr" /><ref name="onclive1" />
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	=== What were the results of the MSKCC CAR-T trial for mesothelioma? ===		=== What were the results of the MSKCC CAR-T trial for mesothelioma? ===

	The MSKCC phase I trial (NCT02414269) achieved ~~groundbreaking results:~~ a 72% ~~overall response rate~~ in patients receiving intrapleural mesothelin-targeted CAR-T cells combined with pembrolizumab, ~~including~~ 2 complete metabolic responses. ~~Among~~ patients ~~receiving lymphodepleting chemotherapy,~~ 12~~-month overall survival reached 80~~.2%. ~~These are~~ the ~~best CAR~~-~~T results ever reported in a solid tumor~~.<ref name="~~ascopost" /><ref name="vbcancer" /><ref name="oncnurse~~" />		The MSKCC phase I trial (NCT02414269) achieved a 23.9-month median overall survival and 83% 1-year OS in 18 mesothelioma patients receiving intrapleural mesothelin-targeted CAR-T cells combined with pembrolizumab, with 2 complete metabolic responses on PET scan. The mRECIST-assessed best response in 16 evaluable patients was 12.5% partial response and 56.3% stable disease. Note: Some secondary sources report a "72% ORR" from this trial, but this figure does not appear in the peer-reviewed publication (PMID 34266984).<ref name="pubmedmskcc" />

	=== Why is CAR-T delivered directly into the chest for mesothelioma? ===		=== Why is CAR-T delivered directly into the chest for mesothelioma? ===

MesotheliomaSupport: ANCHOR content + CLEO QA 91/100 — new page: CAR-T mechanism, mesothelin targeting, MSK results, active trials

2026-04-14T05:03:42Z

ANCHOR content + CLEO QA 91/100 — new page: CAR-T mechanism, mesothelin targeting, MSK results, active trials

Show changes

MesotheliomaSupport: Add NAC-T cells (63.6% ORR, Advanced Science 2025), Gavo-cel Phase 1 (Nature Medicine 2023), expand EVEREST-2 with ASCO 2025 data — ANCHOR-2026-04-13-002

2026-04-13T22:55:32Z

Add NAC-T cells (63.6% ORR, Advanced Science 2025), Gavo-cel Phase 1 (Nature Medicine 2023), expand EVEREST-2 with ASCO 2025 data — ANCHOR-2026-04-13-002

@@ Line 197: / Line 197: @@
 A 2025-initiated National Cancer Institute trial is testing TNhYP218 CAR-T cells, which use a novel anti-mesothelin antibody (hYP218) that binds a membrane-proximal epitope of mesothelin — a fundamentally different binding site than most existing constructs. The trial employs T-naive/stem cell memory (Tnaive/SCM) cell populations designed for improved persistence.<ref name="ncttnhyp" /><ref name="pmchyp218" />
 === Currently Recruiting CAR-T Trials (as of January 2026) ===
@@ Line 379: / Line 431: @@
 === Bispecific and Logic-Gated CARs ===
-Dual-targeting CARs that address two antigens simultaneously represent one of the most promising strategies to prevent antigen-negative tumor escape. The EVEREST-2 trial (NCT06051695) is evaluating a logic-gated mesothelin CAR-T that incorporates HLA-based safety mechanisms, allowing the CAR to distinguish between cancer cells and normal tissues with greater precision than conventional single-target designs.<ref name="pmclogicgate" /><ref name="pmcdual" /><ref name="ascomsln" />
+Dual-targeting CARs that address two antigens simultaneously represent one of the most promising strategies to prevent antigen-negative tumor escape. The EVEREST-2 trial (NCT06051695) is evaluating a logic-gated mesothelin CAR-T (A2B694) that incorporates an HLA-A*02 blocker alongside a mesothelin activator, allowing the CAR to distinguish between cancer cells and normal tissues at single-cell resolution. Initial Phase 1 data presented at ASCO 2025 showed no dose-limiting toxicities or cytokine release syndrome in 5 treated malignant pleural mesothelioma patients, with initial evidence of anti-tumor activity (see [[#EVEREST-2 (A2B694): Logic-Gated Tmod CAR-T (NCT06051695)|EVEREST-2 clinical data above]]).<ref name="pmclogicgate" /><ref name="pmcdual" /><ref name="ascomsln" /><ref name="everest2" />
 === CRISPR-Edited CAR-T ===
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 <ref name="mesoatty">[https://mesotheliomaattorney.com/ Mesothelioma Attorney — Legal Compensation for Asbestos Exposure Victims], MesotheliomaAttorney.com</ref>
 <ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>
 </references>

← Older revision		Revision as of 11:23, 19 April 2026
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	== Overview ==		== Overview ==

	Chimeric antigen receptor T-cell (CAR-T) therapy is an advanced form of [[immunotherapy]] in which a patient's own T cells are genetically engineered to recognize and destroy cancer cells. While CAR-T therapy has transformed the treatment of blood cancers — with six FDA-approved products achieving complete response rates as high as 90% in B-cell acute lymphoblastic leukemia — its application in solid tumors like [[Pleural Mesothelioma\|malignant mesothelioma]] remains in early clinical stages.<ref name="bioinformant" /><ref name="ijpmmm" /> The landmark phase I trial at Memorial Sloan Kettering Cancer Center (MSKCC) demonstrated a median overall survival of 23.9 months using intrapleurally delivered mesothelin-targeted CAR-T cells combined with pembrolizumab, substantially exceeding standard-of-care benchmarks.<ref name="pubmedmskcc" /><ref name="pmcmskcc" /> In 2025, Chinese researchers reported a 63.6% overall response rate with NAC-T cells (nanobody-armored CAR-T), the highest ORR for any mesothelin-targeted cellular therapy in mesothelioma to date. As of April 2026, seven or more CAR-T clinical trials are actively recruiting mesothelioma patients across academic cancer centers worldwide.<ref name="mesowatch" /><ref name="mesonet" />		Chimeric antigen receptor T-cell (CAR-T) therapy is an advanced form of [[immunotherapy]] in which a patient's own T cells are genetically engineered to recognize and destroy cancer cells. While CAR-T therapy has transformed the treatment of blood cancers — with six FDA-approved products achieving complete response rates as high as 90% in B-cell acute lymphoblastic leukemia — its application in solid tumors like [[Pleural Mesothelioma\|malignant mesothelioma]] remains in early clinical stages.<ref name="bioinformant" /><ref name="ijpmmm" /> The landmark phase I trial at Memorial Sloan Kettering Cancer Center (MSKCC) demonstrated a median overall survival of 23.9 months using intrapleurally delivered mesothelin-targeted CAR-T cells combined with pembrolizumab, substantially exceeding standard-of-care benchmarks.<ref name="pubmedmskcc" /><ref name="pmcmskcc" /> In 2025, Chinese researchers reported a 63.6% overall response rate with NAC-T cells (nanobody-armored CAR-T), the highest ORR for any mesothelin-targeted cellular therapy in mesothelioma to date.<ref name="nact" /> As of April 2026, seven or more CAR-T clinical trials are actively recruiting mesothelioma patients across academic cancer centers worldwide.<ref name="mesowatch" /><ref name="mesonet" />

	{\| class="infobox" style="width:280px; float:right; margin:0 0 1em 1em; border:2px solid #1a5276; border-radius:8px; overflow:hidden;"		{\| class="infobox" style="width:280px; float:right; margin:0 0 1em 1em; border:2px solid #1a5276; border-radius:8px; overflow:hidden;"
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	\| style="padding:15px;" \|		\| style="padding:15px;" \|
	* CAR-T cells are a patient's own T cells genetically modified to express a chimeric antigen receptor that recognizes and kills cancer cells without requiring MHC presentation<ref name="pmcantimeso" /><ref name="ijpmmm" />		* CAR-T cells are a patient's own T cells genetically modified to express a chimeric antigen receptor that recognizes and kills cancer cells without requiring MHC presentation<ref name="pmcantimeso" /><ref name="ijpmmm" />
	* Mesothelin is the primary CAR-T target for mesothelioma, overexpressed in approximately '''95% of epithelioid''' pleural mesotheliomas; sarcomatoid mesothelioma shows no detectable MSLN overexpression, limiting this approach to epithelioid and biphasic subtypes<ref name="pmcmsln" />		* Mesothelin is the primary CAR-T target for mesothelioma, overexpressed in approximately '''95% of epithelioid''' pleural mesotheliomas; sarcomatoid mesothelioma shows no detectable MSLN overexpression, limiting this approach to epithelioid and biphasic subtypes<ref name="pmcmsln95" /><ref name="pmcmsln" />
	* The MSKCC phase I trial achieved a '''23.9-month median overall survival''' with intrapleural mesothelin-targeted CAR-T cells combined with pembrolizumab (1-year OS: 83%), with best radiologic response of 12.5% partial response and 56.3% stable disease by mRECIST<ref name="pubmedmskcc" /><ref name="pmcmskcc" />		* The MSKCC phase I trial achieved a '''23.9-month median overall survival''' with intrapleural mesothelin-targeted CAR-T cells combined with pembrolizumab (1-year OS: 83%), with best radiologic response of 12.5% partial response and 56.3% stable disease by mRECIST<ref name="pubmedmskcc" /><ref name="pmcmskcc" />
	* NAC-T cells (anti-PD-1 nanobody-armored CAR-T) achieved a '''63.6% overall response rate''' and '''100% disease control rate''' in 11 mesothelioma patients (2025), the highest response rates reported for any MSLN-targeted CAR-T therapy		* NAC-T cells (anti-PD-1 nanobody-armored CAR-T) achieved a '''63.6% overall response rate''' and '''100% disease control rate''' in 11 mesothelioma patients (2025), the highest response rates reported for any MSLN-targeted CAR-T therapy<ref name="nact" />
	* Intrapleural delivery of CAR-T cells directly into the chest cavity is a key innovation that achieves higher local concentrations and lower systemic toxicity compared to intravenous delivery<ref name="pmcregional" />		* Intrapleural delivery of CAR-T cells directly into the chest cavity is a key innovation that achieves higher local concentrations and lower systemic toxicity compared to intravenous delivery<ref name="pmcregional" />
	* Among 18 MPM patients receiving CAR-T cells followed by pembrolizumab at MSKCC, 1-year overall survival reached 83%, with 2 patients achieving complete metabolic responses on PET lasting 16-26 months<ref name="pubmedmskcc" />		* Among 18 MPM patients receiving CAR-T cells followed by pembrolizumab at MSKCC, 1-year overall survival reached 83%, with 2 patients achieving complete metabolic responses on PET lasting 16-26 months<ref name="pubmedmskcc" />
Line 202:		Line 202:
	=== NAC-T Cells: Nanobody-Armored CAR-T (Advanced Science, October 2025) ===		=== NAC-T Cells: Nanobody-Armored CAR-T (Advanced Science, October 2025) ===

	The most clinically significant 2025 result is the first-in-human trial of '''NAC-T cells''' — anti-PD-1 nanobody-armored mesothelin-targeting CAR-T cells — published in ''Advanced Science'' in October 2025. This Chinese study enrolled 11 patients with advanced malignant mesothelioma who received intravenous NAC-T cell infusions at doses of 5-20 × 10⁶ cells/kg following lymphodepletion.		The most clinically significant 2025 result is the first-in-human trial of '''NAC-T cells''' — anti-PD-1 nanobody-armored mesothelin-targeting CAR-T cells — published in ''Advanced Science'' in October 2025. This Chinese study enrolled 11 patients with advanced malignant mesothelioma who received intravenous NAC-T cell infusions at doses of 5-20 × 10⁶ cells/kg following lymphodepletion.<ref name="nact" />

	The key innovation: these CAR-T cells were engineered to continuously '''secrete anti-PD-1 nanobodies''' into the tumor microenvironment, providing localized checkpoint blockade without systemic anti-PD-1 exposure.		The key innovation: these CAR-T cells were engineered to continuously '''secrete anti-PD-1 nanobodies''' into the tumor microenvironment, providing localized checkpoint blockade without systemic anti-PD-1 exposure.<ref name="nact" />

	Results:		Results:
	* '''Overall response rate: 63.6%''' — 1 complete response and 6 partial responses		* '''Overall response rate: 63.6%''' — 1 complete response and 6 partial responses<ref name="nact" />
	* '''Disease control rate: 100%'''		* '''Disease control rate: 100%'''<ref name="nact" />
	* Median progression-free survival: '''5.0 months'''		* Median progression-free survival: '''5.0 months'''<ref name="nact" />
	* Median overall survival: '''25.6 months'''		* Median overall survival: '''25.6 months'''<ref name="nact" />
	* No dose-limiting toxicity; well-tolerated safety profile		* No dose-limiting toxicity; well-tolerated safety profile<ref name="nact" />

	These results represent the highest response rates reported for any MSLN-targeted CAR-T therapy in mesothelioma. The nanobody secretion strategy delivers checkpoint inhibition precisely where CAR-T cells are active, addressing a core limitation of sequential checkpoint inhibitor administration.		These results represent the highest response rates reported for any MSLN-targeted CAR-T therapy in mesothelioma. The nanobody secretion strategy delivers checkpoint inhibition precisely where CAR-T cells are active, addressing a core limitation of sequential checkpoint inhibitor administration.<ref name="nact" />

	=== EVEREST-2: Logic-Gated Tmod CAR-T (NCT06051695) ===		=== EVEREST-2: Logic-Gated Tmod CAR-T (NCT06051695) ===
Line 223:		Line 223:
	=== Gavo-cel (TC-210): TCR-T Fusion Construct (NCT03907852) ===		=== Gavo-cel (TC-210): TCR-T Fusion Construct (NCT03907852) ===

	'''Gavocabtagene autoleucel (gavo-cel)''' from TCR² Therapeutics uses a TRuC (T-cell Receptor fusion Construct) architecture — an anti-MSLN scFv fused directly to the TCR complex — harnessing natural TCR signaling. Published in ''Nature Medicine'' in July 2023, Phase 1 results in 32 patients (23 mesothelioma) showed:		'''Gavocabtagene autoleucel (gavo-cel)''' from TCR² Therapeutics uses a TRuC (T-cell Receptor fusion Construct) architecture — an anti-MSLN scFv fused directly to the TCR complex — harnessing natural TCR signaling. Published in ''Nature Medicine'' in July 2023, Phase 1 results in 32 patients (23 mesothelioma) showed:<ref name="gavocel" />

	* Disease control rate: '''77%''' across all patients; target lesion regression in 93% of evaluable patients		* Disease control rate: '''77%''' across all patients; target lesion regression in 93% of evaluable patients<ref name="gavocel" />
	* ORR by BICR after lymphodepletion: '''22%''' (mesothelioma subgroup: 21%)		* ORR by BICR after lymphodepletion: '''22%''' (mesothelioma subgroup: 21%)<ref name="gavocel" />
	* Median OS for MPM patients: '''11.2 months'''; median PFS: 5.6 months		* Median OS for MPM patients: '''11.2 months'''; median PFS: 5.6 months<ref name="gavocel" />

	=== Currently Recruiting CAR-T Trials (as of April 2026) ===		=== Currently Recruiting CAR-T Trials (as of April 2026) ===
Line 487:		Line 487:
	<ref name="pmcmsln">[https://pmc.ncbi.nlm.nih.gov/articles/PMC10952516/ High mesothelin expression by immunohistochemistry predicts poor clinical outcomes], PMC (2024)</ref>		<ref name="pmcmsln">[https://pmc.ncbi.nlm.nih.gov/articles/PMC10952516/ High mesothelin expression by immunohistochemistry predicts poor clinical outcomes], PMC (2024)</ref>
	<ref name="pmcmsln2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study], PMC (2021)</ref>		<ref name="pmcmsln2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study], PMC (2021)</ref>
			<ref name="ascopost">[https://ascopost.com/issues/april-25-2019/preliminary-results-show-activity-for-mesothelin-directed-car-t-cell-therapy-in-malignant-mesothelioma/ Preliminary Results Show Activity for Mesothelin-Directed CAR T-Cell Therapy in Malignant Mesothelioma], The ASCO Post (2019)</ref>
	<ref name="ijpmmm">[https://journals.lww.com/10.4103/IJPMMM.IJPMMM_4_25 From concept to cure: CAR T-cell therapy molecular mechanisms, clinical triumphs, and future horizons], Indian Journal of Pathology and Microbiology (2025)</ref>		<ref name="ijpmmm">[https://journals.lww.com/10.4103/IJPMMM.IJPMMM_4_25 From concept to cure: CAR T-cell therapy molecular mechanisms, clinical triumphs, and future horizons], Indian Journal of Pathology and Microbiology (2025)</ref>
	<ref name="pmcfap">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/ Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells], PMC (2021)</ref>		<ref name="pmcfap">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/ Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells], PMC (2021)</ref>
Line 559:		Line 560:
	<ref name="mesoatty">[https://mesotheliomaattorney.com/ Mesothelioma Attorney — Legal Compensation for Asbestos Exposure Victims], MesotheliomaAttorney.com</ref>		<ref name="mesoatty">[https://mesotheliomaattorney.com/ Mesothelioma Attorney — Legal Compensation for Asbestos Exposure Victims], MesotheliomaAttorney.com</ref>
	<ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>		<ref name="mesoatty2">[https://mesotheliomaattorney.com/mesothelioma-settlements/ Mesothelioma Settlements and Legal Options for Treatment Coverage], MesotheliomaAttorney.com</ref>
			<ref name="gavocel">[https://pubmed.ncbi.nlm.nih.gov/37474806/ Gavocabtagene autoleucel (gavo-cel), an autologous anti-mesothelin TRuC-T cell therapy, in patients with mesothelin-expressing cancers: a phase 1 clinical trial], Nature Medicine (2023)</ref>
			<ref name="nact">[https://pubmed.ncbi.nlm.nih.gov/39400460/ Anti-PD-1 nanobody-armored anti-mesothelin CAR-T cells (NAC-T) for malignant mesothelioma: first-in-human results], Advanced Science (2025)</ref>
			<ref name="pmcmsln95">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,448 Tumors], PMC (2021) — reports mesothelin overexpression in approximately 95% of epithelioid pleural mesotheliomas</ref>
	</references>		</references>

← Older revision		Revision as of 11:20, 19 April 2026
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	== Overview ==		== Overview ==

	Chimeric antigen receptor T-cell (CAR-T) therapy is an advanced form of [[immunotherapy]] in which a patient's own T cells are genetically engineered to recognize and destroy cancer cells. While CAR-T therapy has transformed the treatment of blood cancers — with six FDA-approved products achieving complete response rates as high as 90% in B-cell acute lymphoblastic leukemia — its application in solid tumors like [[Pleural Mesothelioma\|malignant mesothelioma]] remains in early clinical stages.<ref name="bioinformant" /><ref name="ijpmmm" /> The landmark phase I trial at Memorial Sloan Kettering Cancer Center (MSKCC) demonstrated a median overall survival of 23.9 months using intrapleurally delivered mesothelin-targeted CAR-T cells combined with pembrolizumab, substantially exceeding standard-of-care benchmarks.<ref name="pubmedmskcc" /><ref name="pmcmskcc" /> In 2025, Chinese researchers reported a 63.6% overall response rate with NAC-T cells (nanobody-armored CAR-T), the highest ORR for any mesothelin-targeted cellular therapy in mesothelioma to date.~~<ref name="nact" />~~ As of April 2026, seven or more CAR-T clinical trials are actively recruiting mesothelioma patients across academic cancer centers worldwide.<ref name="mesowatch" /><ref name="mesonet" />		Chimeric antigen receptor T-cell (CAR-T) therapy is an advanced form of [[immunotherapy]] in which a patient's own T cells are genetically engineered to recognize and destroy cancer cells. While CAR-T therapy has transformed the treatment of blood cancers — with six FDA-approved products achieving complete response rates as high as 90% in B-cell acute lymphoblastic leukemia — its application in solid tumors like [[Pleural Mesothelioma\|malignant mesothelioma]] remains in early clinical stages.<ref name="bioinformant" /><ref name="ijpmmm" /> The landmark phase I trial at Memorial Sloan Kettering Cancer Center (MSKCC) demonstrated a median overall survival of 23.9 months using intrapleurally delivered mesothelin-targeted CAR-T cells combined with pembrolizumab, substantially exceeding standard-of-care benchmarks.<ref name="pubmedmskcc" /><ref name="pmcmskcc" /> In 2025, Chinese researchers reported a 63.6% overall response rate with NAC-T cells (nanobody-armored CAR-T), the highest ORR for any mesothelin-targeted cellular therapy in mesothelioma to date. As of April 2026, seven or more CAR-T clinical trials are actively recruiting mesothelioma patients across academic cancer centers worldwide.<ref name="mesowatch" /><ref name="mesonet" />

	{\| class="infobox" style="width:280px; float:right; margin:0 0 1em 1em; border:2px solid #1a5276; border-radius:8px; overflow:hidden;"		{\| class="infobox" style="width:280px; float:right; margin:0 0 1em 1em; border:2px solid #1a5276; border-radius:8px; overflow:hidden;"
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	\| style="padding:15px;" \|		\| style="padding:15px;" \|
	* CAR-T cells are a patient's own T cells genetically modified to express a chimeric antigen receptor that recognizes and kills cancer cells without requiring MHC presentation<ref name="pmcantimeso" /><ref name="ijpmmm" />		* CAR-T cells are a patient's own T cells genetically modified to express a chimeric antigen receptor that recognizes and kills cancer cells without requiring MHC presentation<ref name="pmcantimeso" /><ref name="ijpmmm" />
	* Mesothelin is the primary CAR-T target for mesothelioma, overexpressed in approximately '''95% of epithelioid''' pleural mesotheliomas; sarcomatoid mesothelioma shows no detectable MSLN overexpression, limiting this approach to epithelioid and biphasic subtypes~~<ref name="pmcmsln95" />~~<ref name="pmcmsln" />		* Mesothelin is the primary CAR-T target for mesothelioma, overexpressed in approximately '''95% of epithelioid''' pleural mesotheliomas; sarcomatoid mesothelioma shows no detectable MSLN overexpression, limiting this approach to epithelioid and biphasic subtypes<ref name="pmcmsln" />
	* The MSKCC phase I trial achieved a '''23.9-month median overall survival''' with intrapleural mesothelin-targeted CAR-T cells combined with pembrolizumab (1-year OS: 83%), with best radiologic response of 12.5% partial response and 56.3% stable disease by mRECIST<ref name="pubmedmskcc" /><ref name="pmcmskcc" />		* The MSKCC phase I trial achieved a '''23.9-month median overall survival''' with intrapleural mesothelin-targeted CAR-T cells combined with pembrolizumab (1-year OS: 83%), with best radiologic response of 12.5% partial response and 56.3% stable disease by mRECIST<ref name="pubmedmskcc" /><ref name="pmcmskcc" />
	* NAC-T cells (anti-PD-1 nanobody-armored CAR-T) achieved a '''63.6% overall response rate''' and '''100% disease control rate''' in 11 mesothelioma patients (2025), the highest response rates reported for any MSLN-targeted CAR-T therapy~~<ref name="nact" />~~		* NAC-T cells (anti-PD-1 nanobody-armored CAR-T) achieved a '''63.6% overall response rate''' and '''100% disease control rate''' in 11 mesothelioma patients (2025), the highest response rates reported for any MSLN-targeted CAR-T therapy
	* Intrapleural delivery of CAR-T cells directly into the chest cavity is a key innovation that achieves higher local concentrations and lower systemic toxicity compared to intravenous delivery<ref name="pmcregional" />		* Intrapleural delivery of CAR-T cells directly into the chest cavity is a key innovation that achieves higher local concentrations and lower systemic toxicity compared to intravenous delivery<ref name="pmcregional" />
	* Among 18 MPM patients receiving CAR-T cells followed by pembrolizumab at MSKCC, 1-year overall survival reached 83%, with 2 patients achieving complete metabolic responses on PET lasting 16-26 months<ref name="pubmedmskcc" />		* Among 18 MPM patients receiving CAR-T cells followed by pembrolizumab at MSKCC, 1-year overall survival reached 83%, with 2 patients achieving complete metabolic responses on PET lasting 16-26 months<ref name="pubmedmskcc" />
Line 202:		Line 202:
	=== NAC-T Cells: Nanobody-Armored CAR-T (Advanced Science, October 2025) ===		=== NAC-T Cells: Nanobody-Armored CAR-T (Advanced Science, October 2025) ===

	The most clinically significant 2025 result is the first-in-human trial of '''NAC-T cells''' — anti-PD-1 nanobody-armored mesothelin-targeting CAR-T cells — published in ''Advanced Science'' in October 2025. This Chinese study enrolled 11 patients with advanced malignant mesothelioma who received intravenous NAC-T cell infusions at doses of 5-20 × 10⁶ cells/kg following lymphodepletion.~~<ref name="nact" />~~		The most clinically significant 2025 result is the first-in-human trial of '''NAC-T cells''' — anti-PD-1 nanobody-armored mesothelin-targeting CAR-T cells — published in ''Advanced Science'' in October 2025. This Chinese study enrolled 11 patients with advanced malignant mesothelioma who received intravenous NAC-T cell infusions at doses of 5-20 × 10⁶ cells/kg following lymphodepletion.

	The key innovation: these CAR-T cells were engineered to continuously '''secrete anti-PD-1 nanobodies''' into the tumor microenvironment, providing localized checkpoint blockade without systemic anti-PD-1 exposure.~~<ref name="nact" />~~		The key innovation: these CAR-T cells were engineered to continuously '''secrete anti-PD-1 nanobodies''' into the tumor microenvironment, providing localized checkpoint blockade without systemic anti-PD-1 exposure.

	Results:		Results:
	* '''Overall response rate: 63.6%''' — 1 complete response and 6 partial responses~~<ref name="nact" />~~		* '''Overall response rate: 63.6%''' — 1 complete response and 6 partial responses
	* '''Disease control rate: 100%'''~~<ref name="nact" />~~		* '''Disease control rate: 100%'''
	* Median progression-free survival: '''5.0 months'''~~<ref name="nact" />~~		* Median progression-free survival: '''5.0 months'''
	* Median overall survival: '''25.6 months'''~~<ref name="nact" />~~		* Median overall survival: '''25.6 months'''
	* No dose-limiting toxicity; well-tolerated safety profile~~<ref name="nact" />~~		* No dose-limiting toxicity; well-tolerated safety profile

	These results represent the highest response rates reported for any MSLN-targeted CAR-T therapy in mesothelioma. The nanobody secretion strategy delivers checkpoint inhibition precisely where CAR-T cells are active, addressing a core limitation of sequential checkpoint inhibitor administration.~~<ref name="nact" />~~		These results represent the highest response rates reported for any MSLN-targeted CAR-T therapy in mesothelioma. The nanobody secretion strategy delivers checkpoint inhibition precisely where CAR-T cells are active, addressing a core limitation of sequential checkpoint inhibitor administration.

	=== EVEREST-2: Logic-Gated Tmod CAR-T (NCT06051695) ===		=== EVEREST-2: Logic-Gated Tmod CAR-T (NCT06051695) ===
Line 223:		Line 223:
	=== Gavo-cel (TC-210): TCR-T Fusion Construct (NCT03907852) ===		=== Gavo-cel (TC-210): TCR-T Fusion Construct (NCT03907852) ===

	'''Gavocabtagene autoleucel (gavo-cel)''' from TCR² Therapeutics uses a TRuC (T-cell Receptor fusion Construct) architecture — an anti-MSLN scFv fused directly to the TCR complex — harnessing natural TCR signaling. Published in ''Nature Medicine'' in July 2023, Phase 1 results in 32 patients (23 mesothelioma) showed:~~<ref name="gavocel" />~~		'''Gavocabtagene autoleucel (gavo-cel)''' from TCR² Therapeutics uses a TRuC (T-cell Receptor fusion Construct) architecture — an anti-MSLN scFv fused directly to the TCR complex — harnessing natural TCR signaling. Published in ''Nature Medicine'' in July 2023, Phase 1 results in 32 patients (23 mesothelioma) showed:

	* Disease control rate: '''77%''' across all patients; target lesion regression in 93% of evaluable patients~~<ref name="gavocel" />~~		* Disease control rate: '''77%''' across all patients; target lesion regression in 93% of evaluable patients
	* ORR by BICR after lymphodepletion: '''22%''' (mesothelioma subgroup: 21%)~~<ref name="gavocel" />~~		* ORR by BICR after lymphodepletion: '''22%''' (mesothelioma subgroup: 21%)
	* Median OS for MPM patients: '''11.2 months'''; median PFS: 5.6 months~~<ref name="gavocel" />~~		* Median OS for MPM patients: '''11.2 months'''; median PFS: 5.6 months

	=== Currently Recruiting CAR-T Trials (as of April 2026) ===		=== Currently Recruiting CAR-T Trials (as of April 2026) ===
Line 487:		Line 487:
	<ref name="pmcmsln">[https://pmc.ncbi.nlm.nih.gov/articles/PMC10952516/ High mesothelin expression by immunohistochemistry predicts poor clinical outcomes], PMC (2024)</ref>		<ref name="pmcmsln">[https://pmc.ncbi.nlm.nih.gov/articles/PMC10952516/ High mesothelin expression by immunohistochemistry predicts poor clinical outcomes], PMC (2024)</ref>
	<ref name="pmcmsln2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study], PMC (2021)</ref>		<ref name="pmcmsln2">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8067734/ Mesothelin Expression in Human Tumors: A Tissue Microarray Study], PMC (2021)</ref>
	<ref name="ascopost">[https://ascopost.com/issues/april-25-2019/preliminary-results-show-activity-for-mesothelin-directed-car-t-cell-therapy-in-malignant-mesothelioma/ Preliminary Results Show Activity for Mesothelin-Directed CAR T-Cell Therapy in Malignant Mesothelioma], The ASCO Post (2019)</ref>
	<ref name="ijpmmm">[https://journals.lww.com/10.4103/IJPMMM.IJPMMM_4_25 From concept to cure: CAR T-cell therapy molecular mechanisms, clinical triumphs, and future horizons], Indian Journal of Pathology and Microbiology (2025)</ref>		<ref name="ijpmmm">[https://journals.lww.com/10.4103/IJPMMM.IJPMMM_4_25 From concept to cure: CAR T-cell therapy molecular mechanisms, clinical triumphs, and future horizons], Indian Journal of Pathology and Microbiology (2025)</ref>
	<ref name="pmcfap">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/ Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells], PMC (2021)</ref>		<ref name="pmcfap">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8354246/ Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells], PMC (2021)</ref>