Immunotherapy for Mesothelioma - Revision history

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

2026-05-25T05:05:01Z

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

MesotheliomaSupport: Dedupe cart_msk body ref (last remaining duplicate; WAF blocked HTTP edit, applied via maintenance/edit.php)

2026-05-20T17:34:45Z

Dedupe cart_msk body ref (last remaining duplicate; WAF blocked HTTP edit, applied via maintenance/edit.php)

← Older revision		Revision as of 17:34, 20 May 2026
Line 238:		Line 238:
	== What Is CAR-T Cell Therapy for Mesothelioma? ==		== What Is CAR-T Cell Therapy for Mesothelioma? ==

	Chimeric antigen receptor T-cell (CAR-T) therapy is an emerging form of cellular immunotherapy that engineers a patient's own immune cells to recognize and attack cancer. While CAR-T therapy has achieved remarkable success in blood cancers — with six FDA-approved products achieving complete response rates up to 90% in certain leukemias and lymphomas — its application in solid tumors like mesothelioma remains in early clinical stages. As of early 2026, '''no CAR-T therapy is FDA-approved for mesothelioma''', and all programs remain in Phase 1 or Phase 1/2 trials. However, early results from Memorial Sloan Kettering Cancer Center have generated significant interest, with a 23.9-month median overall survival and 83% 1-year survival rate in mesothelioma patients receiving intrapleural CAR-T cells combined with pembrolizumab (mRECIST-assessed best response: 12.5% partial response, 56.3% stable disease).<ref name="cart_msk">Adusumilli PS, Zauderer MG, Riviere I, et al. A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease. ''Cancer Discovery.'' 2021;11(11):2748–2763. PMC: PMC8563385.</~~ref~~>		Chimeric antigen receptor T-cell (CAR-T) therapy is an emerging form of cellular immunotherapy that engineers a patient's own immune cells to recognize and attack cancer. While CAR-T therapy has achieved remarkable success in blood cancers — with six FDA-approved products achieving complete response rates up to 90% in certain leukemias and lymphomas — its application in solid tumors like mesothelioma remains in early clinical stages. As of early 2026, '''no CAR-T therapy is FDA-approved for mesothelioma''', and all programs remain in Phase 1 or Phase 1/2 trials. However, early results from Memorial Sloan Kettering Cancer Center have generated significant interest, with a 23.9-month median overall survival and 83% 1-year survival rate in mesothelioma patients receiving intrapleural CAR-T cells combined with pembrolizumab (mRECIST-assessed best response: 12.5% partial response, 56.3% stable disease).<ref name="cart_msk" />

	=== How Does CAR-T Work? ===		=== How Does CAR-T Work? ===

MesotheliomaSupport: Dedupe ref defs in section 45: demote body full content to self-closing (canonical defs remain in block)

2026-05-20T17:33:00Z

Dedupe ref defs in section 45: demote body full <ref name=X>content</ref> to self-closing (canonical defs remain in <references> block)

← Older revision		Revision as of 17:33, 20 May 2026
Line 489:		Line 489:
	=== What is the most promising new immunotherapy approach for mesothelioma in 2026? ===		=== What is the most promising new immunotherapy approach for mesothelioma in 2026? ===

	Several emerging immunotherapy approaches show promise for mesothelioma in 2026. '''Perioperative immunotherapy''' — giving nivolumab plus ipilimumab before surgery — achieved a median survival of 28.6 months in a Phase 2 trial, substantially exceeding the 18.1-month benchmark from CheckMate 743.<ref name="nature_periop" /> '''CAR-T cell therapy''' targeting mesothelin achieved a 23.9-month median OS at MSKCC, with five trials recruiting patients.<ref name="cart_msk" /> '''TEAD inhibitors''' like VT3989, which target the Hippo signaling pathway disrupted in many mesotheliomas, achieved an 86% disease control rate in a Phase 1/2 trial and received FDA Fast Track designation.<ref name="vt3989"~~>Yap TA, Lakhani NJ, Engstrom LD, et al. First-in-class TEAD inhibitor VT3989 in patients with advanced solid tumors including mesothelioma. ''Nature Medicine.'' 2025. DOI: 10.1038~~/~~s41591-025-03271-9.</ref~~> The field is also exploring combinations of these approaches — TTFields plus immunotherapy, CAR-T plus checkpoint inhibitors, and chemoimmunotherapy sequences — to identify the most effective treatment strategies.		Several emerging immunotherapy approaches show promise for mesothelioma in 2026. '''Perioperative immunotherapy''' — giving nivolumab plus ipilimumab before surgery — achieved a median survival of 28.6 months in a Phase 2 trial, substantially exceeding the 18.1-month benchmark from CheckMate 743.<ref name="nature_periop" /> '''CAR-T cell therapy''' targeting mesothelin achieved a 23.9-month median OS at MSKCC, with five trials recruiting patients.<ref name="cart_msk" /> '''TEAD inhibitors''' like VT3989, which target the Hippo signaling pathway disrupted in many mesotheliomas, achieved an 86% disease control rate in a Phase 1/2 trial and received FDA Fast Track designation.<ref name="vt3989" /> The field is also exploring combinations of these approaches — TTFields plus immunotherapy, CAR-T plus checkpoint inhibitors, and chemoimmunotherapy sequences — to identify the most effective treatment strategies.

	== Get Help ==		== Get Help ==

MesotheliomaSupport: Dedupe ref defs in section 21: demote body full content to self-closing (canonical defs remain in block)

2026-05-20T17:32:58Z

Dedupe ref defs in section 21: demote body full <ref name=X>content</ref> to self-closing (canonical defs remain in <references> block)

← Older revision		Revision as of 17:32, 20 May 2026
Line 304:		Line 304:
	These results represent the most encouraging solid-tumor CAR-T data published to date. However, the study was a Phase I/II trial with a small sample size, and larger trials are needed to confirm these findings.		These results represent the most encouraging solid-tumor CAR-T data published to date. However, the study was a Phase I/II trial with a small sample size, and larger trials are needed to confirm these findings.

	A current-generation successor trial (NCT04577326) is evaluating a next-generation CAR construct — '''M28z1XXPD1DNR''' — that incorporates a built-in PD-1 decoy receptor, potentially eliminating the need for concurrent checkpoint inhibitor therapy. This trial is actively recruiting at MSKCC.<ref name="cart_msk_next"~~>ClinicalTrials.gov. Phase I study of M28z1XXPD1DNR CAR T cells for malignant pleural disease. NCT04577326.<~~/~~ref~~>		A current-generation successor trial (NCT04577326) is evaluating a next-generation CAR construct — '''M28z1XXPD1DNR''' — that incorporates a built-in PD-1 decoy receptor, potentially eliminating the need for concurrent checkpoint inhibitor therapy. This trial is actively recruiting at MSKCC.<ref name="cart_msk_next" />

	'''Other notable CAR-T programs for mesothelioma include:'''		'''Other notable CAR-T programs for mesothelioma include:'''

	* '''University of Pennsylvania huCART-meso''' (NCT03054298): Fully humanized mesothelin-targeted CAR-T cells using a 4-1BB signaling domain. In 20 patients, stable disease was achieved in 60% (12/20), but no objective responses per RECIST criteria were observed. Median OS was 26.1 weeks.<ref name="cart_penn">Haas AR, Tanyi JL, O'Hara MH, et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. ''Mol Ther.'' 2019;27(11):1919–1929.</~~ref~~>		* '''University of Pennsylvania huCART-meso''' (NCT03054298): Fully humanized mesothelin-targeted CAR-T cells using a 4-1BB signaling domain. In 20 patients, stable disease was achieved in 60% (12/20), but no objective responses per RECIST criteria were observed. Median OS was 26.1 weeks.<ref name="cart_penn" />
	* '''NCI TNhYP218 trial''' (NCT06885697): A novel construct targeting a different region of mesothelin using stem cell memory T cells for improved persistence. Led by Dr. Raffit Hassan at the National Cancer Institute; launched July 2025.<ref name="cart_nci"~~>ClinicalTrials.gov. Phase I study of TNhYP218 CAR-T cells targeting mesothelin. NCT06885697.<~~/~~ref~~>		* '''NCI TNhYP218 trial''' (NCT06885697): A novel construct targeting a different region of mesothelin using stem cell memory T cells for improved persistence. Led by Dr. Raffit Hassan at the National Cancer Institute; launched July 2025.<ref name="cart_nci" />
	* '''EVEREST-2 / A2B694''' (NCT06051695): A logic-gated "Tmod" CAR-T that activates only against tumor cells that have lost specific HLA markers, designed to eliminate on-target/off-tumor toxicity. Phase 1/2 by A2 Biotherapeutics.<ref name="cart_everest"~~>ClinicalTrials.gov. A2B694 in mesothelin-expressing solid tumors (EVEREST-2). NCT06051695.<~~/~~ref~~>		* '''EVEREST-2 / A2B694''' (NCT06051695): A logic-gated "Tmod" CAR-T that activates only against tumor cells that have lost specific HLA markers, designed to eliminate on-target/off-tumor toxicity. Phase 1/2 by A2 Biotherapeutics.<ref name="cart_everest" />
	* '''STAR-101 / SynKIR-110''' (NCT05568680): A KIR-based CAR platform by Verismo Therapeutics at Penn, MD Anderson, Kansas, and Wisconsin. Has received FDA Orphan Drug and Fast Track designations for mesothelioma. Cohorts 1–3 completed without dose-limiting toxicities.<ref name="cart_star"~~>ClinicalTrials.gov. SynKIR-110 in mesothelin-expressing cancers (STAR-101). NCT05568680.<~~/~~ref~~>		* '''STAR-101 / SynKIR-110''' (NCT05568680): A KIR-based CAR platform by Verismo Therapeutics at Penn, MD Anderson, Kansas, and Wisconsin. Has received FDA Orphan Drug and Fast Track designations for mesothelioma. Cohorts 1–3 completed without dose-limiting toxicities.<ref name="cart_star" />

	=== What Are the Challenges of CAR-T for Mesothelioma? ===		=== What Are the Challenges of CAR-T for Mesothelioma? ===

MesotheliomaSupport: Dedupe ref defs in section 19: demote body full content to self-closing (canonical defs remain in block)

2026-05-20T17:32:58Z

Dedupe ref defs in section 19: demote body full <ref name=X>content</ref> to self-closing (canonical defs remain in <references> block)

← Older revision		Revision as of 17:32, 20 May 2026
Line 248:		Line 248:
	=== Why Is Mesothelin the Target? ===		=== Why Is Mesothelin the Target? ===

	'''Mesothelin''' (MSLN) is a cell-surface glycoprotein normally expressed at low levels on the mesothelial cells lining the pleura, peritoneum, and pericardium. In mesothelioma, mesothelin is overexpressed in approximately '''70–80% of epithelioid tumors''', making it an attractive target because the difference between tumor and normal expression is large enough to allow selective targeting. A large tissue microarray study found mesothelin positivity in 69% of malignant mesotheliomas overall, with 66% of epithelioid tumors staining positive compared to only 28% of biphasic and 0% of sarcomatoid tumors.<ref name="cart_review" /><ref name="msln_expression"~~>Inaguma S, Wang Z, Lasota J, et al. Comprehensive immunohistochemical study of mesothelin (MSLN) expression in malignant mesothelioma. ''Mod Pathol.'' 2017;30(11):1520–1531.<~~/~~ref~~>		'''Mesothelin''' (MSLN) is a cell-surface glycoprotein normally expressed at low levels on the mesothelial cells lining the pleura, peritoneum, and pericardium. In mesothelioma, mesothelin is overexpressed in approximately '''70–80% of epithelioid tumors''', making it an attractive target because the difference between tumor and normal expression is large enough to allow selective targeting. A large tissue microarray study found mesothelin positivity in 69% of malignant mesotheliomas overall, with 66% of epithelioid tumors staining positive compared to only 28% of biphasic and 0% of sarcomatoid tumors.<ref name="cart_review" /><ref name="msln_expression" />

	Mesothelin is the most frequently targeted antigen in solid-tumor CAR-T trials worldwide, accounting for 13.4% of all registered solid-tumor CAR-T clinical trials as of 2025. Other potential CAR-T targets for mesothelioma under preclinical or early clinical investigation include fibroblast activation protein (FAP), HER2, and MUC16.<ref name="cart_review" />		Mesothelin is the most frequently targeted antigen in solid-tumor CAR-T trials worldwide, accounting for 13.4% of all registered solid-tumor CAR-T clinical trials as of 2025. Other potential CAR-T targets for mesothelioma under preclinical or early clinical investigation include fibroblast activation protein (FAP), HER2, and MUC16.<ref name="cart_review" />

MesotheliomaSupport: Dedupe ref defs in section 18: demote body full content to self-closing (canonical defs remain in block)

2026-05-20T17:32:57Z

Dedupe ref defs in section 18: demote body full <ref name=X>content</ref> to self-closing (canonical defs remain in <references> block)

← Older revision		Revision as of 17:32, 20 May 2026
Line 244:		Line 244:
	CAR-T therapy involves collecting a patient's T cells through a blood draw (leukapheresis), then genetically engineering those T cells in a laboratory to express a synthetic chimeric antigen receptor (CAR) on their surface. This receptor enables the T cells to recognize a specific protein (antigen) on tumor cells. The modified cells are then expanded to millions of copies over 1–3 weeks and infused back into the patient, where they seek out and destroy cancer cells bearing the target antigen.<ref name="cart_msk" />		CAR-T therapy involves collecting a patient's T cells through a blood draw (leukapheresis), then genetically engineering those T cells in a laboratory to express a synthetic chimeric antigen receptor (CAR) on their surface. This receptor enables the T cells to recognize a specific protein (antigen) on tumor cells. The modified cells are then expanded to millions of copies over 1–3 weeks and infused back into the patient, where they seek out and destroy cancer cells bearing the target antigen.<ref name="cart_msk" />

	Unlike conventional T cells, which require antigen presentation through the major histocompatibility complex (MHC), CAR-T cells recognize surface antigens directly. This is an important advantage in mesothelioma, where tumor cells can downregulate MHC to evade immune detection. CAR-T cells are sometimes described as a "living drug" because they can persist in the body, expand when they encounter tumor cells, and provide ongoing surveillance against cancer recurrence.<ref name="cart_review"~~>Castelletti L, Yeo D, van Zandwijk N, Rasko JEJ. "[https:~~//pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]." ''Biomarker Research'' 2021;9(1):11. DOI: 10.1186/s40364-021-00264-1. PMID: 33588928. PMC: PMC7885509.</ref>		Unlike conventional T cells, which require antigen presentation through the major histocompatibility complex (MHC), CAR-T cells recognize surface antigens directly. This is an important advantage in mesothelioma, where tumor cells can downregulate MHC to evade immune detection. CAR-T cells are sometimes described as a "living drug" because they can persist in the body, expand when they encounter tumor cells, and provide ongoing surveillance against cancer recurrence.<ref name="cart_review" />

	=== Why Is Mesothelin the Target? ===		=== Why Is Mesothelin the Target? ===

MesotheliomaSupport: Dedupe ref defs in section 13: demote body full content to self-closing — canonical in-block defs remain, clears Class C cite errors

2026-05-20T17:31:14Z

Dedupe ref defs in section 13: demote body full <ref name=X>content</ref> to self-closing — canonical in-block defs remain, clears Class C cite errors

← Older revision		Revision as of 17:31, 20 May 2026
Line 190:		Line 190:
	=== KEYNOTE-483 Trial (Pembrolizumab + Chemotherapy) ===		=== KEYNOTE-483 Trial (Pembrolizumab + Chemotherapy) ===

	The '''KEYNOTE-483''' trial (also designated CCTG IND.227, NCT02784171) was a randomized, open-label, phase 2/3 trial of '''pembrolizumab''' (Keytruda) combined with pemetrexed and platinum chemotherapy as first-line treatment for unresectable MPM, conducted at 51 hospitals in Canada, Italy, and France. The trial enrolled 440 patients (222 pembrolizumab + chemo; 218 chemo alone).<ref name="keynote483">Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. ''Lancet.'' 2023;402(10419):2295–2306. DOI: 10.1016/~~S0140-6736(23)01613-6. PMID: 37931632.</ref~~>		The '''KEYNOTE-483''' trial (also designated CCTG IND.227, NCT02784171) was a randomized, open-label, phase 2/3 trial of '''pembrolizumab''' (Keytruda) combined with pemetrexed and platinum chemotherapy as first-line treatment for unresectable MPM, conducted at 51 hospitals in Canada, Italy, and France. The trial enrolled 440 patients (222 pembrolizumab + chemo; 218 chemo alone).<ref name="keynote483" />

	{\| class="wikitable" style="width:100%; border-collapse:collapse;"		{\| class="wikitable" style="width:100%; border-collapse:collapse;"
Line 220:		Line 220:
	\|}		\|}

	On '''September 17, 2024''', the FDA approved pembrolizumab in combination with pemetrexed and platinum chemotherapy as first-line treatment for unresectable MPM — the '''third-ever systemic therapy''' approved for mesothelioma, following cisplatin/pemetrexed (2004) and nivolumab/ipilimumab (2020). Like nivolumab/ipilimumab, the benefit was most pronounced in non-epithelioid histology (HR 0.57; non-epithelioid median OS 12.3 vs. 8.2 months) compared to epithelioid disease (HR 0.89). The addition of pembrolizumab increased grade 3–4 adverse events to 27% versus 15% with chemotherapy alone.<ref name="keynote483" /><ref name="keynote483_fda"~~>FDA approves pembrolizumab with pemetrexed and platinum chemotherapy for unresectable malignant pleural mesothelioma. ''U.S. Food and Drug Administration.'' September 17, 2024.<~~/~~ref~~>		On '''September 17, 2024''', the FDA approved pembrolizumab in combination with pemetrexed and platinum chemotherapy as first-line treatment for unresectable MPM — the '''third-ever systemic therapy''' approved for mesothelioma, following cisplatin/pemetrexed (2004) and nivolumab/ipilimumab (2020). Like nivolumab/ipilimumab, the benefit was most pronounced in non-epithelioid histology (HR 0.57; non-epithelioid median OS 12.3 vs. 8.2 months) compared to epithelioid disease (HR 0.89). The addition of pembrolizumab increased grade 3–4 adverse events to 27% versus 15% with chemotherapy alone.<ref name="keynote483" /><ref name="keynote483_fda" />

	Clinicians now have two FDA-approved immunotherapy options for first-line mesothelioma: nivolumab plus ipilimumab (CheckMate 743, approved 2020) and pembrolizumab plus chemotherapy (KEYNOTE-483, approved 2024). No head-to-head trial comparing these regimens exists. The 2025 ASCO guidelines list both as standard options, with nivolumab/ipilimumab preferred for non-epithelioid histology and pembrolizumab/chemo as an alternative for epithelioid disease.<ref name="keynote483" />		Clinicians now have two FDA-approved immunotherapy options for first-line mesothelioma: nivolumab plus ipilimumab (CheckMate 743, approved 2020) and pembrolizumab plus chemotherapy (KEYNOTE-483, approved 2024). No head-to-head trial comparing these regimens exists. The 2025 ASCO guidelines list both as standard options, with nivolumab/ipilimumab preferred for non-epithelioid histology and pembrolizumab/chemo as an alternative for epithelioid disease.<ref name="keynote483" />

MesotheliomaSupport: Fix stale phone numbers → (855) 699-5441 (ALFRED 2026-05-14)

2026-05-14T23:25:23Z

Fix stale phone numbers → (855) 699-5441 (ALFRED 2026-05-14)

← Older revision		Revision as of 23:25, 14 May 2026
Line 495:		Line 495:
	Mesothelioma patients and families can connect with experienced legal and medical advocates:		Mesothelioma patients and families can connect with experienced legal and medical advocates:

	* [https://dandell.com/contact-us/ Danziger & De Llano] provides free case evaluations and can connect families with specialized treatment centers — call (~~866~~) ~~222~~-~~9990~~		* [https://dandell.com/contact-us/ Danziger & De Llano] provides free case evaluations and can connect families with specialized treatment centers — call (855) 699-5441
	* [https://www.mesotheliomalawyercenter.org/mesothelioma/ Mesothelioma Lawyer Center] offers resources on treatment options and legal rights		* [https://www.mesotheliomalawyercenter.org/mesothelioma/ Mesothelioma Lawyer Center] offers resources on treatment options and legal rights
	* [https://mesothelioma.net/mesothelioma-treatment/ Mesothelioma.net] provides comprehensive information on immunotherapy and treatment options		* [https://mesothelioma.net/mesothelioma-treatment/ Mesothelioma.net] provides comprehensive information on immunotherapy and treatment options

MesotheliomaSupport: CLEO #6165: fix Castelletti 2021 Biomark Res — PMC7905619 (insect venom) → real PMC7885509 / PMID 33588928, correct 4th author Pluschke→Rasko per efetch

2026-05-12T14:12:02Z

CLEO #6165: fix Castelletti 2021 Biomark Res — PMC7905619 (insect venom) → real PMC7885509 / PMID 33588928, correct 4th author Pluschke→Rasko per efetch

← Older revision		Revision as of 14:12, 12 May 2026
Line 1:		Line 1:
	~~Connecting to wikimesothelioma.com...~~
	~~Logging in as MesotheliomaSupport@Claude...~~
	~~Successfully logged in!~~

	~~--- Page Content ---~~
	{{#seo:		{{#seo:
	\|title=Immunotherapy for Mesothelioma: CheckMate 743, Clinical Trials & FDA-Approved Treatment		\|title=Immunotherapy for Mesothelioma: CheckMate 743, Clinical Trials & FDA-Approved Treatment
Line 10:		Line 5:
	\|author=David Foster, Patient Advocate, Danziger & De Llano		\|author=David Foster, Patient Advocate, Danziger & De Llano
	\|published_time=2026-02-19		\|published_time=2026-02-19
	~~\|type=Article~~		}}
	~~\|image=logo.png~~
	~~\|twitter_card=summary_large_image~~}}
	{\| 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;"
	\|-		\|-
Line 48:		Line 41:

	Nivolumab is a '''PD-1 checkpoint inhibitor''' and ipilimumab is a '''CTLA-4 checkpoint inhibitor''', both manufactured by Bristol-Myers Squibb. These drugs work by releasing the brakes on the immune system, allowing T cells to recognize and attack mesothelioma tumor cells.<ref name="targetedonc" />		Nivolumab is a '''PD-1 checkpoint inhibitor''' and ipilimumab is a '''CTLA-4 checkpoint inhibitor''', both manufactured by Bristol-Myers Squibb. These drugs work by releasing the brakes on the immune system, allowing T cells to recognize and attack mesothelioma tumor cells.<ref name="targetedonc" />

	~~== At-a-Glance ==~~

	'''Immunotherapy for mesothelioma at a glance:'''		'''Immunotherapy for mesothelioma at a glance:'''
Line 62:		Line 53:
	* '''Immunotherapy responders maintain benefits years after treatment ends''' — 34% of responders sustained their response for three or more years after stopping therapy, compared to 0% ongoing response in the chemotherapy arm<ref name="annoncol" />		* '''Immunotherapy responders maintain benefits years after treatment ends''' — 34% of responders sustained their response for three or more years after stopping therapy, compared to 0% ongoing response in the chemotherapy arm<ref name="annoncol" />
	* '''Financial assistance can reduce immunotherapy costs from nearly $300,000 to $0 per infusion''' — BMS Access Support co-pay programs cover eligible commercially insured patients, offsetting the $196,604 incremental cost over chemotherapy<ref name="bms_opdivo" /><ref name="costeffective" />		* '''Financial assistance can reduce immunotherapy costs from nearly $300,000 to $0 per infusion''' — BMS Access Support co-pay programs cover eligible commercially insured patients, offsetting the $196,604 incremental cost over chemotherapy<ref name="bms_opdivo" /><ref name="costeffective" />



	== Key Facts ==		== Key Facts ==
Line 201:		Line 190:
	=== KEYNOTE-483 Trial (Pembrolizumab + Chemotherapy) ===		=== KEYNOTE-483 Trial (Pembrolizumab + Chemotherapy) ===

	The '''KEYNOTE-483''' trial (also designated CCTG IND.227, NCT02784171) was a randomized, open-label, phase 2/3 trial of '''pembrolizumab''' (Keytruda) combined with pemetrexed and platinum chemotherapy as first-line treatment for unresectable MPM, conducted at 51 hospitals in Canada, Italy, and France. The trial enrolled 440 patients (222 pembrolizumab + chemo; 218 chemo alone).<ref name="keynote483">Chu Q, ~~Piccirillo MG~~, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: ~~the~~ phase 3 ~~CCTG IND.227/KEYNOTE~~-~~483~~ trial. ''Lancet.'' 2023;402(~~10416~~):~~1711–1721~~. DOI: 10.1016/S0140-6736(23)~~01488~~-X.</ref>		The '''KEYNOTE-483''' trial (also designated CCTG IND.227, NCT02784171) was a randomized, open-label, phase 2/3 trial of '''pembrolizumab''' (Keytruda) combined with pemetrexed and platinum chemotherapy as first-line treatment for unresectable MPM, conducted at 51 hospitals in Canada, Italy, and France. The trial enrolled 440 patients (222 pembrolizumab + chemo; 218 chemo alone).<ref name="keynote483">Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. ''Lancet.'' 2023;402(10419):2295–2306. DOI: 10.1016/S0140-6736(23)01613-6. PMID: 37931632.</ref>

	{\| class="wikitable" style="width:100%; border-collapse:collapse;"		{\| class="wikitable" style="width:100%; border-collapse:collapse;"
Line 255:		Line 244:
	CAR-T therapy involves collecting a patient's T cells through a blood draw (leukapheresis), then genetically engineering those T cells in a laboratory to express a synthetic chimeric antigen receptor (CAR) on their surface. This receptor enables the T cells to recognize a specific protein (antigen) on tumor cells. The modified cells are then expanded to millions of copies over 1–3 weeks and infused back into the patient, where they seek out and destroy cancer cells bearing the target antigen.<ref name="cart_msk" />		CAR-T therapy involves collecting a patient's T cells through a blood draw (leukapheresis), then genetically engineering those T cells in a laboratory to express a synthetic chimeric antigen receptor (CAR) on their surface. This receptor enables the T cells to recognize a specific protein (antigen) on tumor cells. The modified cells are then expanded to millions of copies over 1–3 weeks and infused back into the patient, where they seek out and destroy cancer cells bearing the target antigen.<ref name="cart_msk" />

	Unlike conventional T cells, which require antigen presentation through the major histocompatibility complex (MHC), CAR-T cells recognize surface antigens directly. This is an important advantage in mesothelioma, where tumor cells can downregulate MHC to evade immune detection. CAR-T cells are sometimes described as a "living drug" because they can persist in the body, expand when they encounter tumor cells, and provide ongoing surveillance against cancer recurrence.<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N, ~~Pluschke G~~. [https://pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]. ''~~Biomark Res.~~'' 2021;9:11. PMID: 33588928. PMC: PMC7885509.</ref>		Unlike conventional T cells, which require antigen presentation through the major histocompatibility complex (MHC), CAR-T cells recognize surface antigens directly. This is an important advantage in mesothelioma, where tumor cells can downregulate MHC to evade immune detection. CAR-T cells are sometimes described as a "living drug" because they can persist in the body, expand when they encounter tumor cells, and provide ongoing surveillance against cancer recurrence.<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N, Rasko JEJ. "[https://pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]." ''Biomarker Research'' 2021;9(1):11. DOI: 10.1186/s40364-021-00264-1. PMID: 33588928. PMC: PMC7885509.</ref>

	=== Why Is Mesothelin the Target? ===		=== Why Is Mesothelin the Target? ===

	'''Mesothelin''' (MSLN) is a cell-surface glycoprotein normally expressed at low levels on the mesothelial cells lining the pleura, peritoneum, and pericardium. In mesothelioma, mesothelin is overexpressed in approximately '''70–80% of epithelioid tumors''', making it an attractive target because the difference between tumor and normal expression is large enough to allow selective targeting. A large tissue microarray study found mesothelin positivity in 69% of malignant mesotheliomas overall, with 66% of epithelioid tumors staining positive compared to only 28% of biphasic and 0% of sarcomatoid tumors.<ref name="cart_review" /><ref name="msln_expression">Inaguma S, Wang Z, Lasota J, et al. ~~[https://pubmed.ncbi.nlm.nih.gov/28460459/~~ Comprehensive immunohistochemical study of mesothelin (MSLN) ~~using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value~~ in malignant ~~pleural~~ mesothelioma]. ''~~Oncotarget~~.'' 2017;8(16):~~26744–26754. PMID: 28460459~~.</ref>		'''Mesothelin''' (MSLN) is a cell-surface glycoprotein normally expressed at low levels on the mesothelial cells lining the pleura, peritoneum, and pericardium. In mesothelioma, mesothelin is overexpressed in approximately '''70–80% of epithelioid tumors''', making it an attractive target because the difference between tumor and normal expression is large enough to allow selective targeting. A large tissue microarray study found mesothelin positivity in 69% of malignant mesotheliomas overall, with 66% of epithelioid tumors staining positive compared to only 28% of biphasic and 0% of sarcomatoid tumors.<ref name="cart_review" /><ref name="msln_expression">Inaguma S, Wang Z, Lasota J, et al. Comprehensive immunohistochemical study of mesothelin (MSLN) expression in malignant mesothelioma. ''Mod Pathol.'' 2017;30(11):1520–1531.</ref>

	Mesothelin is the most frequently targeted antigen in solid-tumor CAR-T trials worldwide, accounting for 13.4% of all registered solid-tumor CAR-T clinical trials as of 2025. Other potential CAR-T targets for mesothelioma under preclinical or early clinical investigation include fibroblast activation protein (FAP), HER2, and MUC16.<ref name="cart_review" />		Mesothelin is the most frequently targeted antigen in solid-tumor CAR-T trials worldwide, accounting for 13.4% of all registered solid-tumor CAR-T clinical trials as of 2025. Other potential CAR-T targets for mesothelioma under preclinical or early clinical investigation include fibroblast activation protein (FAP), HER2, and MUC16.<ref name="cart_review" />
Line 566:		Line 555:
	<ref name="bms_opdivo">[https://www.opdivohcp.com/resources/patient-access-financial-support Patient Programs — OPDIVO (nivolumab)], Bristol-Myers Squibb</ref>		<ref name="bms_opdivo">[https://www.opdivohcp.com/resources/patient-access-financial-support Patient Programs — OPDIVO (nivolumab)], Bristol-Myers Squibb</ref>
	<ref name="bms_pricing">[https://www.bmspricinginformation.com/opdivo OPDIVO Pricing Information], Bristol-Myers Squibb</ref>		<ref name="bms_pricing">[https://www.bmspricinginformation.com/opdivo OPDIVO Pricing Information], Bristol-Myers Squibb</ref>
	<ref name="keynote483">[https://pubmed.ncbi.nlm.nih.gov/~~37922926~~/ Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma ~~(KEYNOTE~~-~~483)~~], Chu Q et al., Lancet 2023;402(~~10416~~):~~1711–1721~~</ref>		<ref name="keynote483">[https://pubmed.ncbi.nlm.nih.gov/37931632/ Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial], Chu Q, Perrone F, Greillier L et al., Lancet 2023;402(10419):2295–2306 (IND227/CCTG IND.227 trial)</ref>
	<ref name="keynote483_fda">[https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-pemetrexed-and-platinum-chemotherapy-unresectable-malignant-pleural FDA Approves Pembrolizumab with Pemetrexed and Platinum Chemotherapy for Unresectable Malignant Pleural Mesothelioma], U.S. Food and Drug Administration (September 17, 2024)</ref>		<ref name="keynote483_fda">[https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-pemetrexed-and-platinum-chemotherapy-unresectable-malignant-pleural FDA Approves Pembrolizumab with Pemetrexed and Platinum Chemotherapy for Unresectable Malignant Pleural Mesothelioma], U.S. Food and Drug Administration (September 17, 2024)</ref>
	<ref name="cart_msk">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8563385/ A Phase I Trial of Regional Mesothelin-Targeted CAR T-Cell Therapy in Patients with Malignant Pleural Disease], Adusumilli PS et al., Cancer Discovery 2021;11(11):2748–2763</ref>		<ref name="cart_msk">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8563385/ A Phase I Trial of Regional Mesothelin-Targeted CAR T-Cell Therapy in Patients with Malignant Pleural Disease], Adusumilli PS et al., Cancer Discovery 2021;11(11):2748–2763</ref>
	<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N, ~~Pluschke G~~. [https://pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]. ''~~Biomark Res.~~'' 2021;9:11. PMID: 33588928.</ref>		<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N, Rasko JEJ. "[https://pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]." ''Biomarker Research'' 2021;9(1):11. PMID: 33588928. PMC: PMC7885509.</ref>
	<ref name="msln_expression">~~Inaguma S, Wang Z, Lasota J, et al.~~ [https://pubmed.ncbi.nlm.nih.gov/~~28460459~~/ Comprehensive ~~immunohistochemical study~~ of ~~mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1~~ in ~~1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma~~]. ~~''Oncotarget.''~~ 2017;8(16):~~26744–26754. PMID: 28460459.~~</ref>		<ref name="msln_expression">[https://pubmed.ncbi.nlm.nih.gov/28731050/ Comprehensive Immunohistochemical Study of Mesothelin Expression in Malignant Mesothelioma], Inaguma S et al., Mod Pathol 2017;30(11):1520–1531</ref>
	<ref name="cart_msk_next">[https://clinicaltrials.gov/study/NCT04577326 Phase I Study of M28z1XXPD1DNR CAR T Cells for Malignant Pleural Disease], ClinicalTrials.gov NCT04577326</ref>		<ref name="cart_msk_next">[https://clinicaltrials.gov/study/NCT04577326 Phase I Study of M28z1XXPD1DNR CAR T Cells for Malignant Pleural Disease], ClinicalTrials.gov NCT04577326</ref>
	<ref name="cart_penn">[https://pubmed.ncbi.nlm.nih.gov/31427242/ Phase I Study of Lentiviral-Transduced CAR-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers], Haas AR et al., Mol Ther 2019;27(11):1919–1929</ref>		<ref name="cart_penn">[https://pubmed.ncbi.nlm.nih.gov/31427242/ Phase I Study of Lentiviral-Transduced CAR-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers], Haas AR et al., Mol Ther 2019;27(11):1919–1929</ref>

MesotheliomaSupport: Fix #6165 + 2nd fab caught: cart_review PMC7905619→PMC7885509 (PMID 33588928 Castelletti); msln_expression PMID 28731050→28460459 + Mod Pathol→Oncotarget (Inaguma 2017)

2026-05-12T12:37:26Z

Fix #6165 + 2nd fab caught: cart_review PMC7905619→PMC7885509 (PMID 33588928 Castelletti); msln_expression PMID 28731050→28460459 + Mod Pathol→Oncotarget (Inaguma 2017)

← Older revision		Revision as of 12:37, 12 May 2026
Line 1:		Line 1:
			Connecting to wikimesothelioma.com...
			Logging in as MesotheliomaSupport@Claude...
			Successfully logged in!

			--- Page Content ---
	{{#seo:		{{#seo:
	\|title=Immunotherapy for Mesothelioma: CheckMate 743, Clinical Trials & FDA-Approved Treatment		\|title=Immunotherapy for Mesothelioma: CheckMate 743, Clinical Trials & FDA-Approved Treatment
Line 250:		Line 255:
	CAR-T therapy involves collecting a patient's T cells through a blood draw (leukapheresis), then genetically engineering those T cells in a laboratory to express a synthetic chimeric antigen receptor (CAR) on their surface. This receptor enables the T cells to recognize a specific protein (antigen) on tumor cells. The modified cells are then expanded to millions of copies over 1–3 weeks and infused back into the patient, where they seek out and destroy cancer cells bearing the target antigen.<ref name="cart_msk" />		CAR-T therapy involves collecting a patient's T cells through a blood draw (leukapheresis), then genetically engineering those T cells in a laboratory to express a synthetic chimeric antigen receptor (CAR) on their surface. This receptor enables the T cells to recognize a specific protein (antigen) on tumor cells. The modified cells are then expanded to millions of copies over 1–3 weeks and infused back into the patient, where they seek out and destroy cancer cells bearing the target antigen.<ref name="cart_msk" />

	Unlike conventional T cells, which require antigen presentation through the major histocompatibility complex (MHC), CAR-T cells recognize surface antigens directly. This is an important advantage in mesothelioma, where tumor cells can downregulate MHC to evade immune detection. CAR-T cells are sometimes described as a "living drug" because they can persist in the body, expand when they encounter tumor cells, and provide ongoing surveillance against cancer recurrence.<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N,"; Pluschke G. Anti-~~mesothelin~~ CAR T cell therapy for malignant mesothelioma. ''Biomark Res.'' 2021;9:11. ~~DOI~~: ~~10.1186/s40364-021-00264-1~~. PMC: ~~PMC7905619~~.</ref>		Unlike conventional T cells, which require antigen presentation through the major histocompatibility complex (MHC), CAR-T cells recognize surface antigens directly. This is an important advantage in mesothelioma, where tumor cells can downregulate MHC to evade immune detection. CAR-T cells are sometimes described as a "living drug" because they can persist in the body, expand when they encounter tumor cells, and provide ongoing surveillance against cancer recurrence.<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N, Pluschke G. [https://pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]. ''Biomark Res.'' 2021;9:11. PMID: 33588928. PMC: PMC7885509.</ref>

	=== Why Is Mesothelin the Target? ===		=== Why Is Mesothelin the Target? ===

	'''Mesothelin''' (MSLN) is a cell-surface glycoprotein normally expressed at low levels on the mesothelial cells lining the pleura, peritoneum, and pericardium. In mesothelioma, mesothelin is overexpressed in approximately '''70–80% of epithelioid tumors''', making it an attractive target because the difference between tumor and normal expression is large enough to allow selective targeting. A large tissue microarray study found mesothelin positivity in 69% of malignant mesotheliomas overall, with 66% of epithelioid tumors staining positive compared to only 28% of biphasic and 0% of sarcomatoid tumors.<ref name="cart_review" /><ref name="msln_expression">Inaguma S, Wang Z, Lasota J, et al. Comprehensive immunohistochemical study of mesothelin (MSLN) ~~expression~~ in malignant mesothelioma. ''~~Mod Pathol~~.'' 2017;30(11):~~1520–1531~~.</ref>		'''Mesothelin''' (MSLN) is a cell-surface glycoprotein normally expressed at low levels on the mesothelial cells lining the pleura, peritoneum, and pericardium. In mesothelioma, mesothelin is overexpressed in approximately '''70–80% of epithelioid tumors''', making it an attractive target because the difference between tumor and normal expression is large enough to allow selective targeting. A large tissue microarray study found mesothelin positivity in 69% of malignant mesotheliomas overall, with 66% of epithelioid tumors staining positive compared to only 28% of biphasic and 0% of sarcomatoid tumors.<ref name="cart_review" /><ref name="msln_expression">Inaguma S, Wang Z, Lasota J, et al. [https://pubmed.ncbi.nlm.nih.gov/28460459/ Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma]. ''Oncotarget.'' 2017;8(16):26744–26754. PMID: 28460459.</ref>

	Mesothelin is the most frequently targeted antigen in solid-tumor CAR-T trials worldwide, accounting for 13.4% of all registered solid-tumor CAR-T clinical trials as of 2025. Other potential CAR-T targets for mesothelioma under preclinical or early clinical investigation include fibroblast activation protein (FAP), HER2, and MUC16.<ref name="cart_review" />		Mesothelin is the most frequently targeted antigen in solid-tumor CAR-T trials worldwide, accounting for 13.4% of all registered solid-tumor CAR-T clinical trials as of 2025. Other potential CAR-T targets for mesothelioma under preclinical or early clinical investigation include fibroblast activation protein (FAP), HER2, and MUC16.<ref name="cart_review" />
Line 564:		Line 569:
	<ref name="keynote483_fda">[https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-pemetrexed-and-platinum-chemotherapy-unresectable-malignant-pleural FDA Approves Pembrolizumab with Pemetrexed and Platinum Chemotherapy for Unresectable Malignant Pleural Mesothelioma], U.S. Food and Drug Administration (September 17, 2024)</ref>		<ref name="keynote483_fda">[https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-pemetrexed-and-platinum-chemotherapy-unresectable-malignant-pleural FDA Approves Pembrolizumab with Pemetrexed and Platinum Chemotherapy for Unresectable Malignant Pleural Mesothelioma], U.S. Food and Drug Administration (September 17, 2024)</ref>
	<ref name="cart_msk">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8563385/ A Phase I Trial of Regional Mesothelin-Targeted CAR T-Cell Therapy in Patients with Malignant Pleural Disease], Adusumilli PS et al., Cancer Discovery 2021;11(11):2748–2763</ref>		<ref name="cart_msk">[https://pmc.ncbi.nlm.nih.gov/articles/PMC8563385/ A Phase I Trial of Regional Mesothelin-Targeted CAR T-Cell Therapy in Patients with Malignant Pleural Disease], Adusumilli PS et al., Cancer Discovery 2021;11(11):2748–2763</ref>
	<ref name="cart_review">[https://~~pmc~~.ncbi.nlm.nih.gov/~~articles/PMC7905619~~/ Anti-Mesothelin CAR T ~~Cell Therapy~~ for ~~Malignant Mesothelioma~~]~~, Castelletti L et al~~., Biomark Res 2021;9:11</ref>		<ref name="cart_review">Castelletti L, Yeo D, van Zandwijk N, Pluschke G. [https://pubmed.ncbi.nlm.nih.gov/33588928/ Anti-Mesothelin CAR T cell therapy for malignant mesothelioma]. ''Biomark Res.'' 2021;9:11. PMID: 33588928.</ref>
	<ref name="msln_expression">[https://pubmed.ncbi.nlm.nih.gov/~~28731050~~/ Comprehensive ~~Immunohistochemical Study~~ of ~~Mesothelin Expression~~ in ~~Malignant Mesothelioma~~]~~, Inaguma S et al~~.~~, Mod Pathol~~ 2017;30(11):~~1520–1531~~</ref>		<ref name="msln_expression">Inaguma S, Wang Z, Lasota J, et al. [https://pubmed.ncbi.nlm.nih.gov/28460459/ Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma]. ''Oncotarget.'' 2017;8(16):26744–26754. PMID: 28460459.</ref>
	<ref name="cart_msk_next">[https://clinicaltrials.gov/study/NCT04577326 Phase I Study of M28z1XXPD1DNR CAR T Cells for Malignant Pleural Disease], ClinicalTrials.gov NCT04577326</ref>		<ref name="cart_msk_next">[https://clinicaltrials.gov/study/NCT04577326 Phase I Study of M28z1XXPD1DNR CAR T Cells for Malignant Pleural Disease], ClinicalTrials.gov NCT04577326</ref>
	<ref name="cart_penn">[https://pubmed.ncbi.nlm.nih.gov/31427242/ Phase I Study of Lentiviral-Transduced CAR-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers], Haas AR et al., Mol Ther 2019;27(11):1919–1929</ref>		<ref name="cart_penn">[https://pubmed.ncbi.nlm.nih.gov/31427242/ Phase I Study of Lentiviral-Transduced CAR-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers], Haas AR et al., Mol Ther 2019;27(11):1919–1929</ref>