View source for Mesothelin CAR-T Therapy Mesothelioma

{{#seo:
|title=Mesothelin CAR-T Therapy for Mesothelioma: Penn huCART-meso Phase 1 and the Clinical-Trial Landscape
|description=Penn Abramson Phase 1 (NCT03054298; PMID 41566776) of fully human anti-mesothelin CAR-T (huCART-meso); MSKCC intrapleural and NCI gavo-cel comparators.
|keywords=mesothelin CAR-T, huCART-meso, Penn Abramson, Barber-Rotenberg, NCT03054298, MSKCC NCT02414269, gavo-cel NCT03907852, fully human scFv, MSLN, Carl June, mesothelioma immunotherapy, malignant pleural mesothelioma clinical trial
|author=David Foster, Executive Director of Client Services
|published_time=2026-05-24
}}

= Mesothelin CAR-T Therapy for Mesothelioma =

''Comprehensive medical reference on mesothelin-targeted CAR-T cell therapy in malignant pleural mesothelioma (MPM), anchored on [https://pubmed.ncbi.nlm.nih.gov/41566776/ the Penn Abramson Phase 1 study of autologous T cells bearing fully human chimeric antigen receptors targeting mesothelin in mesothelin-expressing cancers] (''Molecular Therapy'', 2026). This page is educational and is not medical advice. Treatment decisions belong to a patient's oncology team.''

{| class="wikitable" style="float:right; margin:0 0 1em 1em; width:330px; border:2px solid #1a5276;"
! colspan="2" style="background:#1a5276; color:white; text-align:center; padding:10px;" | Penn huCART-meso Phase 1 — at a glance
|-
| style="padding:8px;" | '''Anchor publication'''
| style="padding:8px;" | Barber-Rotenberg JS et al., ''Mol Ther'' 2026 May; PMID 41566776<ref name="penn_phase1" />
|-
| style="padding:8px;" | '''Trial registry'''
| style="padding:8px;" | NCT03054298 — ''CAR T Cells in Mesothelin Expressing Cancers'' (Penn / Abramson Cancer Center)<ref name="nct03054298" />
|-
| style="padding:8px;" | '''Sponsor'''
| style="padding:8px;" | University of Pennsylvania; collaborators: NIH, Tmunity Therapeutics
|-
| style="padding:8px;" | '''Construct'''
| style="padding:8px;" | Fully human anti-mesothelin scFv, 4-1BB / CD3ζ signaling (lentiviral)
|-
| style="padding:8px;" | '''Routes'''
| style="padding:8px;" | Intravenous, intrapleural, intraperitoneal (multi-route)
|-
| style="padding:8px;" | '''Enrollment'''
| style="padding:8px;" | 20 patients (5 MPM, 14 ovarian, 1 lung adeno)
|-
| style="padding:8px;" | '''Dose (MTD)'''
| style="padding:8px;" | 1–3 × 10<sup>7</sup> CAR<sup>+</sup> cells/m<sup>2</sup>
|-
| style="padding:8px;" | '''Best overall response'''
| style="padding:8px;" | Stable disease in 12/20 (60%); 0 CR / 0 PR; max tumor volume reduction 41%
|-
| style="padding:8px;" | '''CRS (any grade)'''
| style="padding:8px;" | 35% (7/20) — most common serious AE
|-
| style="padding:8px;" | '''T-cell persistence'''
| style="padding:8px;" | 16/20 at Day 21; 5/20 at 12 months; 1 patient > 2 years
|-
| style="padding:8px;" | '''Median OS / PFS'''
| style="padding:8px;" | 26.1 weeks / 12.3 weeks
|}

== Executive Summary ==

In May 2026, [https://www.cell.com/molecular-therapy/home ''Molecular Therapy''] published the Phase 1 results of Penn Abramson Cancer Center's '''huCART-meso''' program — autologous T cells engineered with a '''fully human''' anti-mesothelin chimeric antigen receptor (CAR) and a 4-1BB / CD3ζ signaling backbone (Barber-Rotenberg JS, Haas AR, Aggarwal C, O'Hara M, Hexner E, et al., PMID 41566776).<ref name="penn_phase1" /> The trial, registered as '''[https://clinicaltrials.gov/study/NCT03054298 NCT03054298]''', enrolled 20 patients with mesothelin-expressing cancers — 5 with malignant pleural mesothelioma (MPM), 14 with ovarian cancer, and 1 with lung adenocarcinoma — and tested intravenous, intrapleural, and intraperitoneal delivery, with or without cyclophosphamide-based lymphodepletion.<ref name="nct03054298" />

The Phase 1 established the '''feasibility and safety''' of huCART-meso at a Maximum Tolerated Dose of 1–3 × 10<sup>7</sup> CAR<sup>+</sup> cells/m<sup>2</sup>. Two higher-dose cohorts (3 × 10<sup>8</sup> cells/m<sup>2</sup>) were closed during the study after dose-limiting toxicities. Cytokine release syndrome (CRS) was the most common serious adverse event, occurring in 35% of patients (7/20).<ref name="penn_phase1" /> Best overall response was '''stable disease in 12/20 patients (60%)''' with a maximum target-lesion reduction of 41%. Median overall survival was 26.1 weeks and median progression-free survival was 12.3 weeks.<ref name="penn_phase1" /> A key biological finding was the durability of the fully human construct: '''huCART-meso cells were detectable in 16/20 patients at Day 21''', in 5/20 at 12 months, and in one patient beyond two years — substantially longer in vivo persistence than reported for earlier murine-scFv CAR-T-meso programs at the same institution.<ref name="penn_phase1" /><ref name="haas_2019" />

For comparison and broader context — including FDA-approved checkpoint-inhibitor regimens such as nivolumab + ipilimumab and pembrolizumab + chemotherapy — see [[Mesothelioma_Immunotherapy]]. For the DNA-methylation–driven biomarker work that increasingly informs immunotherapy selection in MPM, see [[Mesothelioma_DNA_Methylation_Subtypes_Immunotherapy]]. CAR-T is not an approved mesothelioma therapy in 2026; the trial activity described here is investigational and is delivered only on registered clinical trials at the institutions listed below.

== At a Glance ==

'''Penn huCART-meso Phase 1 (NCT03054298) at a glance:'''

* '''Anchor publication''' — Barber-Rotenberg JS, Haas AR, Aggarwal C, O'Hara M, Hexner E, et al., ''Molecular Therapy'' (May 2026; PMID 41566776) — Phase 1 of autologous T cells bearing fully human chimeric antigen receptors targeting mesothelin in mesothelin-expressing cancers.<ref name="penn_phase1" />
* '''Trial registry''' — [https://clinicaltrials.gov/study/NCT03054298 NCT03054298], ''CAR T Cells in Mesothelin Expressing Cancers'', University of Pennsylvania / Abramson Cancer Center (PI: Janos L. Tanyi, MD, PhD).<ref name="nct03054298" />
* '''Construct''' — fully human anti-mesothelin single-chain variable fragment (scFv) with 4-1BB and CD3ζ signaling domains; lentivirally transduced autologous T cells (huCART-meso).<ref name="penn_phase1" />
* '''Administration routes''' — intravenous, intrapleural (via indwelling pleural catheter), and intraperitoneal — with or without cyclophosphamide-based lymphodepletion.<ref name="nct03054298" />
* '''Enrollment''' — 20 patients in the analyzed cohort: 5 with malignant pleural mesothelioma (MPM), 14 with ovarian cancer, 1 with lung adenocarcinoma.<ref name="penn_phase1" />
* '''Maximum Tolerated Dose''' — 1–3 × 10<sup>7</sup> CAR<sup>+</sup> cells/m<sup>2</sup>; higher-dose cohorts at 3 × 10<sup>8</sup> CAR<sup>+</sup> cells/m<sup>2</sup> were permanently closed during the study after dose-limiting toxicities.<ref name="penn_phase1" />
* '''Best overall response''' — stable disease in 12/20 patients (60%); 0 complete responses, 0 partial responses; maximum target-lesion reduction 41% in a single best responder.<ref name="penn_phase1" />
* '''Cytokine release syndrome''' — 35% (7/20) — most common serious adverse event; graded per the [https://www.astctjournal.org/article/S1083-8791(18)31691-4/fulltext 2019 ASTCT Consensus] (Lee DW, Santomasso BD, Locke FL, et al.).<ref name="penn_phase1" /><ref name="lee_astct_2019" />
* '''T-cell persistence''' — 16/20 patients detectable at Day 21 (80%); 5/20 at 12 months; '''1 patient detectable beyond 2 years''' — the longest reported persistence in the Penn mesothelin CAR-T program.<ref name="penn_phase1" />
* '''Median overall survival''' — 26.1 weeks (≈ 6.5 months); '''median progression-free survival''' — 12.3 weeks (≈ 3 months).<ref name="penn_phase1" />
* '''Comparator landscape''' — Memorial Sloan Kettering intrapleural CAR-T ([https://clinicaltrials.gov/study/NCT02414269 NCT02414269], iCASPM safety switch); NCI gavocabtagene autoleucel "gavo-cel" ([https://clinicaltrials.gov/study/NCT03907852 NCT03907852], TCR-mimetic anti-MSLN construct, ATA Therapeutics / TCR² platform); next-generation Tn-glycosylated MSLN epitope construct '''TNhYP218'''.
* '''Approval status''' — CAR-T is '''not''' an FDA-approved mesothelioma therapy in 2026; all activity described is investigational and is delivered only on registered clinical trials.

== Key Facts ==

{| class="wikitable" style="width:100%; margin:1em 0; border-collapse:collapse; border:2px solid #1a5276;"
|-
! style="background:#1a5276; color:white; padding:12px; text-align:left; width:40%;" | Measure
! style="background:#1a5276; color:white; padding:12px; text-align:left;" | Finding (Source)
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Anchor publication
| style="padding:10px; border-bottom:1px solid #dee2e6;" | Barber-Rotenberg JS et al., ''Molecular Therapy'' May 2026 (PMID 41566776)<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Trial registry / sponsor
| style="padding:10px; border-bottom:1px solid #dee2e6;" | NCT03054298 — University of Pennsylvania / Abramson Cancer Center; collaborators NIH, Tmunity Therapeutics<ref name="nct03054298" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | CAR construct
| style="padding:10px; border-bottom:1px solid #dee2e6;" | Fully human anti-MSLN scFv; 4-1BB / CD3ζ signaling; lentiviral transduction<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Administration routes
| style="padding:10px; border-bottom:1px solid #dee2e6;" | Intravenous, intrapleural, intraperitoneal — ± cyclophosphamide lymphodepletion<ref name="nct03054298" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Enrollment
| style="padding:10px; border-bottom:1px solid #dee2e6;" | '''20 patients''' — 5 MPM, 14 ovarian, 1 lung adenocarcinoma<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Maximum Tolerated Dose
| style="padding:10px; border-bottom:1px solid #dee2e6;" | '''1–3 × 10<sup>7</sup> CAR<sup>+</sup> cells/m<sup>2</sup>'''; 3 × 10<sup>8</sup> cohorts closed for DLT<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Best overall response
| style="padding:10px; border-bottom:1px solid #dee2e6;" | '''Stable disease 12/20 (60%)'''; 0 CR / 0 PR; max target-lesion reduction 41%<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | CRS (any grade)
| style="padding:10px; border-bottom:1px solid #dee2e6;" | '''35% (7/20)''' — graded per ASTCT consensus<ref name="penn_phase1" /><ref name="lee_astct_2019" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | T-cell persistence
| style="padding:10px; border-bottom:1px solid #dee2e6;" | 16/20 at Day 21; 5/20 at 12 mo; '''1 patient > 2 years'''<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Median overall survival
| style="padding:10px; border-bottom:1px solid #dee2e6;" | '''26.1 weeks''' (≈ 6.5 months)<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Median progression-free survival
| style="padding:10px; border-bottom:1px solid #dee2e6;" | '''12.3 weeks''' (≈ 3 months)<ref name="penn_phase1" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Predecessor program (lentiviral, murine scFv)
| style="padding:10px; border-bottom:1px solid #dee2e6;" | Haas AR et al., ''Mol Ther'' 2019 (PMID 31420241) — NCT02159716, n=15, persistence limited by anti-CAR immunity<ref name="haas_2019" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Foundational target paper
| style="padding:10px; border-bottom:1px solid #dee2e6;" | Chang K, Pastan I, ''PNAS'' 1996 (PMID 8552591) — molecular cloning of mesothelin<ref name="chang_pastan_1996" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Tumor-expression map (12,679 tumors)
| style="padding:10px; border-bottom:1px solid #dee2e6;" | Weidemann S et al., ''Biomedicines'' 2021 (PMID 33917081) — MSLN highest in ovarian serous + pancreatic; epithelioid MPM intermediate-to-high<ref name="weidemann_2021" />
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Approval status (2026)
| style="padding:10px; border-bottom:1px solid #dee2e6;" | CAR-T is '''not''' an approved mesothelioma therapy; investigational only on registered trials
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Active comparator trials
| style="padding:10px; border-bottom:1px solid #dee2e6;" | MSKCC intrapleural (NCT02414269, iCASPM); NCI gavo-cel (NCT03907852, TCR-mimetic); next-gen TNhYP218 (Tn-glycosylated MSLN epitope)
|}

== What Is Mesothelin and Why Is It a CAR-T Target? ==

Mesothelin (gene symbol '''MSLN''', chromosome 16p13.3) was first cloned and characterized in [https://pubmed.ncbi.nlm.nih.gov/8552591/ the 1996 PNAS paper on the molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers] (Chang K, Pastan I; PMID 8552591).<ref name="chang_pastan_1996" /> The MSLN precursor is proteolytically cleaved into a ~40 kDa cell-surface glycoprotein (membrane-anchored mesothelin) and a ~31 kDa secreted fragment, megakaryocyte potentiating factor (MPF). In normal tissues, MSLN expression is restricted largely to mesothelial linings of the pleural, peritoneal, and pericardial cavities — a narrow normal-tissue footprint that has made mesothelin one of the most actively pursued targets in solid-tumor CAR-T development.

=== Expression Across Tumor Types ===

A [https://pubmed.ncbi.nlm.nih.gov/33917081/ tissue microarray analysis of 12,679 tumors across 122 tumor types] published by Weidemann et al. in ''Biomedicines'' (2021; PMID 33917081) provides one of the most comprehensive cross-tumor mesothelin maps to date, with very high MSLN positivity in ovarian serous carcinoma and pancreatic ductal adenocarcinoma, intermediate-to-high positivity in epithelioid mesothelioma, and low expression across most non-mesothelial normal tissues.<ref name="weidemann_2021" /> In published series of malignant pleural mesothelioma, mesothelin is broadly expressed in the epithelioid subtype; expression in sarcomatoid mesothelioma is materially lower, and the sarcomatoid component of biphasic disease typically does not stain for MSLN.<ref name="weidemann_2021" /> The exclusion criteria of NCT03054298 reflect this — the trial restricts enrollment by mesothelin expression and excludes patients whose disease is predominantly sarcomatoid.<ref name="nct03054298" />

=== Soluble Mesothelin and the MESOMARK Assay ===

Mesothelin shedding by membrane-anchored proteases releases the extracellular domain into serum and effusion fluid as '''soluble mesothelin-related peptides (SMRP)'''. The [https://www.fda.gov/medical-devices Fujirebio MESOMARK] assay, an FDA-cleared in vitro diagnostic, measures SMRP and is used for monitoring patients with mesothelioma. SMRP elevations correlate with tumor burden and are most useful for tracking response and recurrence rather than primary diagnosis. Soluble mesothelin in the tumor microenvironment can also function as a '''decoy''' that engages anti-mesothelin therapeutics before they reach the tumor surface — a recognized resistance mechanism that influences the design of next-generation constructs targeting non-shed (juxtamembrane) epitopes.

=== Why Mesothelin Is Attractive as a CAR Target ===

The clinical rationale for mesothelin-targeted CAR-T in mesothelioma rests on three factors: (1) restricted normal-tissue distribution limits the off-tumor target landscape mainly to mesothelial surfaces — pleura, peritoneum, pericardium — which are surgically accessible and observable on imaging; (2) high prevalence and density of MSLN in the dominant epithelioid mesothelioma subtype provides an antigen-rich tumor target; (3) the failure of most cytotoxic regimens beyond first-line nivolumab + ipilimumab and pemetrexed-based chemotherapy combinations leaves a long-standing need for adoptive cellular therapy options — a need that [[Mesothelioma_Immunotherapy]] reviews in detail. The principal countervailing concern, discussed in the safety section below, is the same restricted-but-not-absent expression of MSLN on normal mesothelium that gives mesothelin-targeted CAR-T the potential to cause on-target / off-tumor injury to pleural, peritoneal, and pericardial surfaces.

== The Fully Human CAR Construct: Engineering Rationale ==

A chimeric antigen receptor combines an extracellular antibody-derived antigen-recognition module (a single-chain variable fragment, scFv), a hinge / transmembrane region, and intracellular signaling domains (typically a costimulatory domain such as 4-1BB or CD28, plus the CD3ζ activation domain). The scFv determines what the CAR recognizes; the costimulatory architecture and the cell-manufacturing process determine how the resulting CAR-T cell expands, persists, and differentiates in vivo.

=== Why scFv Origin Matters ===

CAR scFvs derived from '''murine''' (mouse) antibody libraries — most prominently the '''SS1''' anti-mesothelin scFv used in the earliest Penn mesothelin CAR-T programs — carry rodent protein sequences that the human immune system can recognize as foreign. Documented consequences include anti-CAR antibody formation and accelerated rejection of infused CAR-T cells, both of which shorten in vivo persistence and limit the feasibility of repeat dosing. The Penn group reported a striking safety event in [https://aacrjournals.org/cancerimmunolres/article/1/1/26/465727 a 2013 report that T cells expressing chimeric antigen receptors can cause anaphylaxis in humans], a study of four patients treated with autologous T cells electroporated with mRNA coding for a chimeric antigen receptor derived from a murine antibody to human mesothelin (Maus MV, Haas AR, Beatty GL, et al., ''Cancer immunology research'' 2013).<ref name="maus_2013" /> Because mRNA expression of the CAR was transient, patients received repeated infusions; one patient developed '''anaphylaxis and cardiac arrest within minutes of completing the third infusion''' — the first description of clinical anaphylaxis from CAR-modified T cells, attributed to IgE antibodies specific to the murine CAR.<ref name="maus_2013" /> The Penn group's [https://aacrjournals.org/cancerimmunolres/article/2/2/112/466262 companion 2014 paper on mesothelin-specific chimeric antigen receptor mRNA-engineered T cells inducing anti-tumor activity in solid malignancies] (Beatty GL, Haas AR, Maus MV, et al., ''Cancer immunology research'' 2014) used the same in-vitro-transcribed mRNA platform — a CAR with CD3ζ and 4-1BB co-stimulatory domains — and demonstrated that adoptive transfer of CARTmeso cells was feasible and safe in mesothelin-expressing solid tumors, with transient peripheral-blood persistence, migration to primary and metastatic mesothelioma sites, and laboratory evidence of antitumor activity including epitope spreading.<ref name="beatty_2014" />

''Humanized'' scFvs (murine framework with grafted human complementarity-determining regions) reduce — but do not eliminate — immunogenicity. ''Fully human'' scFvs, derived end-to-end from human antibody libraries (e.g., phage display, transgenic human-Ig mice), in principle remove the rodent epitopes that drive anti-CAR antibody responses. The huCART-meso construct in NCT03054298 is a fully human anti-mesothelin scFv with 4-1BB and CD3ζ signaling — the same costimulatory architecture used in the first FDA-approved CD19 CAR-T cells, including tisagenlecleucel.<ref name="penn_phase1" /> The persistence data from the Phase 1 (5/20 patients detectable at 12 months; one patient detectable beyond two years) is consistent with the immunogenicity-reduction rationale: the fully human construct does not appear to be rapidly cleared by host immunity in the manner reported for earlier murine-scFv generations at the same institution.<ref name="penn_phase1" /><ref name="haas_2019" />

=== Penn's CART-meso Lineage Before huCART-meso ===

Before the fully human Phase 1, Penn published two important lentiviral CART-meso studies using non-fully-human scFvs in mesothelioma and other mesothelin-expressing solid tumors. The first was the foundational mRNA-engineered Phase 1 case series in 2014 ([https://aacrjournals.org/cancerimmunolres/article/2/2/112/466262 Beatty et al., ''Cancer immunology research'' 2014]), which demonstrated transient CAR expression with no clinical responses but also confirmed feasibility and provided the safety platform on which the program built.<ref name="beatty_2014" /> The second was the [https://pubmed.ncbi.nlm.nih.gov/31420241/ Phase I lentiviral-transduced CART-meso study] published in ''Molecular Therapy'' in 2019 (Haas AR, Tanyi JL, O'Hara MH, et al., PMID 31420241), which enrolled 15 patients with mesothelioma, ovarian cancer, and pancreatic cancer at Penn under [https://clinicaltrials.gov/study/NCT02159716 NCT02159716] — best overall response was stable disease in approximately 11/15 patients, with no durable objective responses and persistence limited in part by anti-CAR immune responses to the murine scFv.<ref name="haas_2019" /> The 2026 fully human construct is the direct response to those persistence findings.

== Penn Phase 1: What the Study Found ==

''All clinical data in this section trace directly to Barber-Rotenberg et al., ''Molecular Therapy'' 2026 (PMID 41566776) and to the public ClinicalTrials.gov record for NCT03054298. Statements that are paraphrased from the published abstract are cited to PMID 41566776; trial-registry detail is cited to NCT03054298.''<ref name="penn_phase1" /><ref name="nct03054298" />

=== Trial Design ===

NCT03054298 is a Phase 1, single-institution, dose-escalation study at the University of Pennsylvania's Abramson Cancer Center. The primary endpoint is the number of participants with treatment-related adverse events as assessed by [https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm CTCAE] v4.03 across a 7-year monitoring window; secondary endpoints include progression-free survival, overall survival, and objective response rate at six months.<ref name="nct03054298" /> The principal investigator of record is Janos L. Tanyi, MD, PhD (Department of Obstetrics and Gynecology, Penn Medicine), and the Phase 1 enrolled patients across three administration routes — '''intravenous, intrapleural via indwelling pleural catheter, and intraperitoneal''' — with or without cyclophosphamide-based lymphodepletion.

=== Patient Population ===

Enrollment was 20 patients in the analyzed cohort, distributed as '''5 patients with malignant pleural mesothelioma''', '''14 patients with ovarian cancer''', and '''1 patient with lung adenocarcinoma'''.<ref name="penn_phase1" /> The numerical predominance of ovarian cancer reflects the Phase 1 multi-tumor feasibility design; the MPM subgroup is small and was not powered for disease-specific efficacy. Mesothelin expression by IHC was required for eligibility, and patients with predominantly sarcomatoid mesothelioma were excluded.<ref name="nct03054298" />

=== Dose and Route ===

The Maximum Tolerated Dose was '''1–3 × 10<sup>7</sup> CAR<sup>+</sup> cells/m<sup>2</sup>'''. Higher-dose cohorts at 3 × 10<sup>8</sup> CAR<sup>+</sup> cells/m<sup>2</sup> were '''permanently closed during the study after dose-limiting toxicities were identified''', a decision that directly informed the final selection of the MTD for the analyzed cohort.<ref name="penn_phase1" /><ref name="nct03054298" /> Lymphodepletion regimens used in the study included cyclophosphamide 1 g/m<sup>2</sup>; intraperitoneal cohorts received cyclophosphamide 300 mg/m<sup>2</sup>/day × 3 days plus fludarabine 30 mg/m<sup>2</sup>/day × 3 days. Some early cohorts received huCART-meso without any lymphodepleting conditioning.<ref name="nct03054298" />

=== Safety ===

'''Cytokine release syndrome''' (CRS) was the most common serious adverse event and occurred in '''7/20 patients (35%)'''.<ref name="penn_phase1" /> Grading distribution at the individual-patient level requires full-text access; the abstract reports the overall incidence as 35% of enrolled patients. CRS in this trial is graded against the [https://www.astctjournal.org/article/S1083-8791(18)31691-4/fulltext 2019 ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells] (Lee DW, Santomasso BD, Locke FL, et al., ''Biology of blood and marrow transplantation'' 2019).<ref name="lee_astct_2019" /> The ASTCT consensus was developed because earlier CRS and neurologic-toxicity grading systems used in CAR-T cell therapy trials for hematologic malignancies and solid tumors — and across many immune-effector-cell immunotherapies in clinical development for both hematologic and solid tumor malignancies including mesothelioma — varied considerably across clinical trials and institutions, making cross-product safety comparisons difficult; field experts convened on June 20–21, 2018 to harmonize the definitions, and the resulting ASTCT criteria are now the standard scale used in mesothelin CAR-T trials including the Penn huCART-meso Phase 1.<ref name="lee_astct_2019" /> The closure of the 3 × 10<sup>8</sup> cells/m<sup>2</sup> cohorts indicates dose-limiting toxicities were observed at the higher dose level; the abstract does not disaggregate those events by grade or organ system.

=== Efficacy ===

Best overall response was '''stable disease in 12/20 patients (60%)''' with a maximum target-lesion reduction of 41% in a single best responder. No complete or partial responses were reported. '''Median overall survival was 26.1 weeks''' (approximately 6.5 months) and '''median progression-free survival was 12.3 weeks''' (approximately 3 months).<ref name="penn_phase1" /> The published abstract presents the trial as establishing feasibility, safety, and preliminary efficacy of huCART-meso and as providing a rationale for future combination trials.

=== T-Cell Persistence ===

Peak in vivo expansion occurred '''within the first 14 days''' after infusion. huCART-meso cells were detectable in '''16/20 patients at Day 21''' (80%) and in '''5/20 patients at 12 months'''. '''One patient had detectable huCART-meso cells beyond two years''' — the longest reported persistence in the Penn mesothelin CAR-T program to date.<ref name="penn_phase1" /> This persistence profile contrasts with the limited persistence reported for the earlier murine-scFv lentiviral CART-meso program ([https://pubmed.ncbi.nlm.nih.gov/31420241/ Haas et al. 2019, PMID 31420241]).<ref name="haas_2019" />

== The Penn Abramson Mesothelin CAR-T Program ==

The huCART-meso Phase 1 is the latest published step in a fifteen-year academic CAR-T program at Penn focused on mesothelin-expressing solid tumors. The program began with mRNA-engineered T-cell case work in mesothelioma in the early 2010s (Beatty GL, Maus MV, Haas AR), moved through lentiviral-transduced CART-meso in mesothelioma, ovarian cancer, and pancreatic cancer (Haas AR, Tanyi JL, O'Hara MH, [https://pubmed.ncbi.nlm.nih.gov/31420241/ PMID 31420241]), and reached the fully human construct described above in NCT03054298.<ref name="beatty_2014" /><ref name="haas_2019" /> The Center for Cellular Immunotherapies (CCI) at Penn — where the program is housed — also developed [https://www.cellularimmunotherapies.org tisagenlecleucel] (Kymriah), the first FDA-approved CAR-T product (CD19 CAR-T for relapsed/refractory B-cell ALL), in collaboration with Novartis. Carl H. June, MD and Bruce L. Levine, PhD are senior figures in both the CD19 and the mesothelin CAR-T programs at Penn.

=== NCI P01 Program Project Grant ===

Mesothelin CAR-T research at Penn has been supported in part by an NCI Program Project Grant (P01) awarded in 2018 to Penn's '''Translational Center of Excellence for Lung Cancer Immunology''' (PI: Steven M. Albelda, MD), a $10.7 million 5-year award supporting integrated work on anti-mesothelin and anti-FAP CAR-T cells, in vivo CAR-T tracking, and bystander immune activation in non-small cell lung cancer and malignant pleural mesothelioma. The grant context is described in NCI and Penn institutional materials and is referenced in the corresponding-author affiliations of PMID 41566776.<ref name="penn_phase1" />

=== Key Penn Investigators (huCART-meso Phase 1) ===

The PMID 41566776 author list includes investigators across Penn's Center for Cellular Immunotherapies (CCI), Abramson Cancer Center, and Departments of Medicine and Obstetrics and Gynecology. Major figures named on the publication include Julie S. Barber-Rotenberg, PhD; Andrew R. Haas, MD, PhD; Charu Aggarwal, MD, MPH; Mark O'Hara, MD; Elizabeth Hexner, MD; Janos L. Tanyi, MD, PhD (principal investigator of NCT03054298); Carl H. June, MD; Bruce L. Levine, PhD; and Steven M. Albelda, MD.<ref name="penn_phase1" />

== Comparator Trials: Where huCART-meso Sits in the Landscape ==

Mesothelin-targeted cell therapy in 2026 is an academic-and-biotech landscape with several distinct architectures and delivery strategies. The three most informative comparators for the Penn fully human IV-and-multi-route trial are summarized below.

=== MSKCC Intrapleural CAR-T — NCT02414269 ===

[https://clinicaltrials.gov/study/NCT02414269 NCT02414269] is the Memorial Sloan Kettering Cancer Center Phase I/II trial of intrapleural mesothelin-targeted CAR-T cells, led by Prasad S. Adusumilli, MD. Patients receive the CAR-T product through an indwelling pleural catheter rather than intravenously, and a subset has been treated with anti-PD-1 pembrolizumab in combination. The trial's headline efficacy signal — reported in conference presentations and institutional materials — is a substantial objective response rate in the mesothelioma subgroup who received cyclophosphamide preconditioning, CAR-T, and pembrolizumab. The MSKCC construct uses a humanized scFv with a CD28 / CD3ζ signaling backbone, delivered by retroviral vector. The architectural contrast with huCART-meso is sharp: '''regional intrapleural delivery''' at MSKCC vs. '''systemic intravenous delivery''' at Penn; '''CD28-costimulated humanized scFv''' at MSKCC vs. '''4-1BB-costimulated fully human scFv''' at Penn; and at MSKCC, '''checkpoint-inhibitor combination''' has been an integral part of the design.

=== Gavocabtagene Autoleucel (Gavo-cel; TC-210) — NCT03907852 ===

[https://clinicaltrials.gov/study/NCT03907852 NCT03907852] is the multi-center Phase 1/2 trial of '''gavocabtagene autoleucel (gavo-cel; TC-210)''' in patients with treatment-refractory mesothelin-expressing solid tumors. Gavo-cel is mechanistically distinct from a conventional CAR: it is a T cell receptor fusion construct (TRuC) consisting of a single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) complex and engages the signaling capacity of the entire TCR upon mesothelin binding — rather than relying on a synthetic CD3ζ-based CAR backbone. Hassan R, Butler M, O'Cearbhaill RE, et al. published [https://www.nature.com/articles/s41591-023-02452-y the Phase 1 interim results of this mesothelin-targeting TRuC cell therapy in refractory mesothelin-expressing solid tumors including mesothelioma, ovarian cancer, and cholangiocarcinoma] in ''Nature medicine'' in 2023.<ref name="hassan_gavocel_2023" /> The primary objectives were safety and the recommended Phase 2 dose (RP2D); secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n=3) or after lymphodepletion (LD, n=29). The trial reported '''dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage''' at higher dose levels — a fatal pulmonary event in the mesothelin TRuC program that, combined with the Penn huCART-meso high-dose cohort closures, has shaped dose selection across the mesothelin cell-therapy field.<ref name="hassan_gavocel_2023" /> The RP2D was determined as 1 × 10<sup>8</sup> cells/m<sup>2</sup> after LD. In '''30 evaluable patients (of 32 enrolled)''', the trial reported a 20% objective response rate (13% confirmed) and a 77% disease control rate; the abstract reports a 6-month overall survival rate of 70% (full-text subgroup OS values such as 10.6 months median in specific dose / LD cohorts require full-text access). Grade ≥3 pneumonitis occurred in 16% of all patients and in none at the RP2D; Grade ≥3 cytokine release syndrome occurred in 25% of all patients and in 15% at the RP2D.<ref name="hassan_gavocel_2023" />

=== NCI TNhYP218 — NCT06885697 ===

[https://clinicaltrials.gov/study/NCT06885697 NCT06885697] is an NCI Phase 1 trial of '''TNhYP218 CAR T cells''' — a naïve / stem-cell-memory mesothelin CAR-T product — for advanced mesothelin-positive solid tumors, including epithelioid mesothelioma (and biphasic mesothelioma with > 80% epithelioid component). Eligibility includes ≥ 50% MSLN positivity on tumor IHC. The trial is conducted at the NIH Clinical Center in Bethesda, Maryland, and was actively enrolling as of mid-2025. The TNhYP218 program is a deliberate effort to use a less-differentiated starting T-cell population in an effort to extend in vivo persistence — an objective that overlaps with the persistence-rationale for the Penn fully human scFv but uses a different lever (T-cell phenotype rather than CAR scFv engineering).

=== Side-by-Side Comparison ===

{| class="wikitable" style="width:100%; margin:1em 0;"
|-
! Trial !! NCT !! PMID (Phase 1) !! Phase !! N !! Route !! Construct !! ORR (MPM) !! mOS !! Notable toxicity
|-
| '''Penn huCART-meso''' || NCT03054298 || 41566776 || I || 20 (5 MPM) || IV / intrapleural / intraperitoneal || Fully human scFv; 4-1BB / CD3ζ (lentiviral) || 0 CR / 0 PR; 60% SD || 26.1 weeks || CRS 35%; high-dose cohorts closed
|-
| '''MSKCC intrapleural''' || NCT02414269 || (conference; not yet primary PMID) || I/II || ≈ 27 || Intrapleural || Humanized scFv; CD28 / CD3ζ (retroviral) ± pembrolizumab || Substantial in pembrolizumab cohort (institutional data) || Not yet primary peer-reviewed || Low-grade CRS reported
|-
| '''Gavo-cel (NCI / TCR2)''' || NCT03907852 || [https://www.nature.com/articles/s41591-023-02452-y Nat Med 2023] || I/II || 32 enrolled / 30 evaluable || IV || Anti-MSLN single-domain TRuC || 20% (13% confirmed) || 6-mo OS 70% (per abstract) || Grade 5 pulmonary hemorrhage at high dose; 25% Grade ≥3 CRS (all) / 15% RP2D
|-
| '''NCI TNhYP218''' || NCT06885697 || — || I || up to 100 || IV || Anti-MSLN CAR on naïve / SCM T cells || Not yet available || Not yet available || Enrolling
|}

== Safety Considerations Specific to Mesothelin CAR-T ==

Cytokine release syndrome — graded against the [https://www.astctjournal.org/article/S1083-8791(18)31691-4/fulltext 2019 ASTCT consensus criteria] (Lee et al., ''Biology of blood and marrow transplantation'' 2019)<ref name="lee_astct_2019" /> — is the dominant immediate safety signal across mesothelin CAR-T programs. Beyond CRS, the safety profile that differentiates mesothelin CAR-T from CD19 or BCMA CAR-T (which target B-lineage and plasma-cell antigens, respectively) is the '''on-target / off-tumor''' risk to '''normal mesothelial surfaces''' — pleura, peritoneum, and pericardium. NCT03054298 excludes patients with clinically significant pericardial effusion in part because mesothelin-induced pericarditis is anticipated as a potential class effect.<ref name="nct03054298" /> Penn's permanent closure of the 3 × 10<sup>8</sup> cells/m<sup>2</sup> cohorts and the gavo-cel Grade 5 pulmonary event at the highest dose level both reflect this narrow therapeutic window.<ref name="penn_phase1" /><ref name="hassan_gavocel_2023" />

A class-level FDA action also bears on the long-term safety conversation: in April 2024, the U.S. Food and Drug Administration required a [https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous boxed warning regarding T-cell malignancies] on all approved autologous CD19- and BCMA-directed CAR-T products, following case reports of secondary T-cell cancers in CAR-T recipients. NCT03054298's 7-year adverse-event monitoring window is consistent with the FDA expectation that lentiviral CAR-T programs surveil for late integration-related malignancies in the years after infusion.<ref name="nct03054298" />

== Manufacturing and Access ==

huCART-meso is manufactured at Penn's '''Clinical Cell and Vaccine Production Facility (CVPF)''', the on-campus GMP cell-therapy facility that has supported Penn's CD19 and other CAR-T programs since the early 2010s. Manufacturing for NCT03054298 follows a standard autologous lentiviral CAR-T workflow: leukapheresis to collect patient T cells, lentiviral transduction with the fully human mesothelin CAR construct, ex vivo expansion in GMP culture, formulation, and cryopreservation pending bedside infusion after lymphodepletion. Because huCART-meso is investigational, access is limited to enrollment on NCT03054298 — patients pursuing the trial must be evaluated at Penn Medicine in Philadelphia, and not all patients with mesothelin-expressing tumors will meet eligibility criteria (notably, sarcomatoid mesothelioma is excluded). For investigational mesothelin CAR-T options at other centers, see the comparator table above.

== What This Means for Patients ==

Mesothelin CAR-T is not an approved mesothelioma treatment in 2026 — the Penn huCART-meso, MSKCC intrapleural, NCI gavo-cel, and TNhYP218 programs are all delivered exclusively on registered clinical trials with strict eligibility criteria. For patients with malignant pleural mesothelioma seeking trial information, the decision pathway typically begins with the patient's treating oncology team and may include:

* Confirming '''histology and subtype''' — most mesothelin CAR-T programs prioritize epithelioid disease and exclude predominantly sarcomatoid mesothelioma;
* '''Mesothelin expression''' — IHC scoring on archival tumor tissue is generally required, with thresholds varying by protocol;
* Performance status and adequacy of organ function for lymphodepleting chemotherapy and cell-therapy infusion;
* Geographic proximity to a trial-conducting center (Penn for huCART-meso; MSKCC for intrapleural CAR-T; NIH Clinical Center for TNhYP218; multiple centers for completed gavo-cel cohorts);
* Practical logistics including the apheresis-to-infusion manufacturing interval and travel for multi-week monitoring.

For broader context on the place of cell therapy alongside FDA-approved checkpoint inhibitors and chemotherapy in MPM, see [[Mesothelioma_Immunotherapy]]. For background on tumor-biology biomarkers that increasingly inform immunotherapy selection in mesothelioma, see [[Mesothelioma_DNA_Methylation_Subtypes_Immunotherapy]]. Patients seeking guidance on how mesothelin CAR-T fits into a broader treatment plan can also consult [[Pleural_Mesothelioma]] for disease-level context.

== Frequently Asked Questions ==

=== Is mesothelin CAR-T an approved treatment for mesothelioma in 2026? ===

No. All mesothelin-targeted CAR-T programs in 2026 — Penn huCART-meso (NCT03054298), MSKCC intrapleural CAR-T (NCT02414269), NCI / TCR2 gavo-cel (NCT03907852), and NCI TNhYP218 (NCT06885697) — are investigational and delivered exclusively on registered clinical trials. There is no FDA-approved mesothelin-targeted cell therapy for mesothelioma at the time of publication.

=== What did the Penn huCART-meso Phase 1 actually show? ===

PMID 41566776 reports feasibility and safety in 20 patients (5 mesothelioma, 14 ovarian, 1 lung adenocarcinoma) at a Maximum Tolerated Dose of 1–3 × 10<sup>7</sup> CAR<sup>+</sup> cells/m<sup>2</sup>; higher-dose cohorts were closed for dose-limiting toxicities. The best overall response was stable disease in 60% of patients with a maximum tumor-volume reduction of 41%; no complete or partial responses were reported. Median overall survival was 26.1 weeks and median progression-free survival was 12.3 weeks. The most distinctive finding was durable T-cell persistence — 16/20 patients at Day 21, 5/20 at 12 months, and one patient beyond two years — consistent with the immunogenicity-reduction rationale for using a fully human scFv.<ref name="penn_phase1" />

=== Why does "fully human" scFv matter? ===

Earlier mesothelin CAR-T programs that used murine-derived (mouse) scFvs documented anti-CAR antibody responses and accelerated immune clearance of the infused cells (Maus et al. 2013; Beatty et al. 2014; Haas et al. 2019, PMID 31420241).<ref name="maus_2013" /><ref name="beatty_2014" /><ref name="haas_2019" /> A fully human scFv is intended to remove the rodent epitopes that drive that response, allowing the CAR-T cells to persist longer and — in principle — providing a better substrate for combination therapy or repeat dosing.

=== What is the difference between the Penn and MSKCC mesothelin CAR-T trials? ===

The Penn huCART-meso Phase 1 (NCT03054298) used '''intravenous, intrapleural, and intraperitoneal''' delivery of a '''fully human scFv''' CAR with '''4-1BB / CD3ζ''' signaling. The MSKCC trial (NCT02414269) uses '''intrapleural-only''' delivery of a '''humanized scFv''' CAR with '''CD28 / CD3ζ''' signaling, with a subset of patients receiving '''pembrolizumab''' in combination. Both programs are investigational; the architectural differences reflect deliberate experimental choices, not refinements of a single design.

=== What is on-target / off-tumor toxicity, and why does it matter for mesothelin CAR-T? ===

Because mesothelin is normally expressed on the cells lining the pleural, peritoneal, and pericardial surfaces, mesothelin-targeted CAR-T cells can in principle engage normal mesothelium and cause inflammation in those compartments — pleuritis, peritonitis, or pericarditis. NCT03054298 excludes patients with significant pericardial effusion in part because of this anticipated class effect, and the closure of the high-dose cohorts and the gavo-cel Grade 5 pulmonary event at high dose are clinical signals consistent with a narrow therapeutic window driven in part by on-target / off-tumor mesothelial engagement.<ref name="penn_phase1" /><ref name="nct03054298" /><ref name="hassan_gavocel_2023" />

=== How is cytokine release syndrome graded? ===

The Penn trial and most contemporary CAR-T programs grade cytokine release syndrome against the 2019 American Society for Transplantation and Cellular Therapy consensus criteria (Lee DW, Santomasso BD, Locke FL, et al., ''Biology of blood and marrow transplantation'' 2019).<ref name="lee_astct_2019" /> Grades range from 1 (fever ≥ 38 °C) to 5 (death). The 35% any-grade CRS rate in PMID 41566776 is consistent with solid-tumor CAR-T programs administering cells systemically.

=== Where can I find related coverage? ===

* [[Mesothelioma_Immunotherapy]] — FDA-approved checkpoint-inhibitor regimens (nivolumab + ipilimumab; pembrolizumab + chemo) and the place of cell therapy
* [[Mesothelioma_DNA_Methylation_Subtypes_Immunotherapy]] — biomarker-driven immunotherapy stratification including adjacent CAR / cell-therapy context
* [[Pleural_Mesothelioma]] — disease-level background for patients evaluating cell-therapy trials

== Get Help ==

<span data-nosnippet class="noai-content">
Mesothelin-targeted CAR-T cell therapy is investigational and available only on clinical trials at the institutions listed above. Patients and families seeking information about clinical-trial eligibility for mesothelioma should consult their treating oncology team and the [https://clinicaltrials.gov ClinicalTrials.gov] registry directly. For questions about navigating mesothelioma diagnosis, treatment options, and patient-support resources alongside trial decisions, the firm's no-fee patient support line is available at '''(855) 699-5441'''.
</span>

== Related Pages ==

* [[Mesothelioma_Immunotherapy|Mesothelioma Immunotherapy]] — FDA-approved checkpoint inhibitor regimens and where cell therapy fits
* [[Mesothelioma_DNA_Methylation_Subtypes_Immunotherapy|Mesothelioma DNA Methylation Subtypes and Immunotherapy]] — biomarker prediction of immunotherapy response
* [[Pleural_Mesothelioma|Pleural Mesothelioma]] — disease-level overview
* [[Mesothelioma_Clinical_Trials|Mesothelioma Clinical Trials]] — broader trial landscape (if available; otherwise [[Mesothelioma_Treatment]])

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    "Weidemann S, Gagelmann P, Gorbokon N, et al. Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors. Biomedicines. 2021;9(4):397. PMID 33917081",
    "Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. (Transplantation and Cellular Therapy)",
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== References ==
<references>
<ref name="penn_phase1">Barber-Rotenberg JS, Haas AR, Aggarwal C, O'Hara M, Hexner E, et al. ''Phase 1 study of autologous T cells bearing fully human chimeric antigen receptors targeting mesothelin in mesothelin-expressing cancers.'' Molecular therapy : the journal of the American Society of Gene Therapy. 2026 May;34(5):2653–2665. DOI: 10.1016/j.ymthe.2026.01.021. [https://pubmed.ncbi.nlm.nih.gov/41566776/ PMID 41566776]</ref>
<ref name="nct03054298">ClinicalTrials.gov, [https://clinicaltrials.gov/study/NCT03054298 NCT03054298 — CAR T Cells in Mesothelin Expressing Cancers]. Sponsor: University of Pennsylvania; principal investigator: Janos L. Tanyi, MD, PhD.</ref>
<ref name="chang_pastan_1996">Chang K, Pastan I. ''Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers.'' Proc Natl Acad Sci USA. 1996 Jan 9;93(1):136–140. [https://pubmed.ncbi.nlm.nih.gov/8552591/ PMID 8552591]</ref>
<ref name="maus_2013">Maus MV, Haas AR, Beatty GL, et al. ''T cells expressing chimeric antigen receptors can cause anaphylaxis in humans.'' Cancer immunology research. 2013 Jul;1(1):26–31. [https://aacrjournals.org/cancerimmunolres/article/1/1/26/465727 AACR Journals]</ref>
<ref name="beatty_2014">Beatty GL, Haas AR, Maus MV, et al. ''Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies.'' Cancer immunology research. 2014 Feb;2(2):112–120. [https://aacrjournals.org/cancerimmunolres/article/2/2/112/466262 AACR Journals]</ref>
<ref name="haas_2019">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 Nov 6;27(11):1919–1929. [https://pubmed.ncbi.nlm.nih.gov/31420241/ PMID 31420241]</ref>
<ref name="weidemann_2021">Weidemann S, Gagelmann P, Gorbokon N, et al. ''Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors.'' Biomedicines. 2021 Apr 7;9(4):397. [https://pubmed.ncbi.nlm.nih.gov/33917081/ PMID 33917081]</ref>
<ref name="lee_astct_2019">Lee DW, Santomasso BD, Locke FL, et al. ''ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.'' Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019 Apr;25(4):625–638. [https://www.astctjournal.org/article/S1083-8791(18)31691-4/fulltext Transplantation and Cellular Therapy Journal]</ref>
<ref name="hassan_gavocel_2023">Hassan R, Butler M, O'Cearbhaill RE, et al. ''Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors.'' Nature medicine. 2023 Aug;29(8):2099–2109. [https://www.nature.com/articles/s41591-023-02452-y Nature Medicine]</ref>
</references>

[[Category:Medical Reviewed]]
[[Category:Mesothelioma Immunotherapy]]
[[Category:CAR-T Cell Therapy]]
[[Category:Mesothelin]]
[[Category:Clinical Trials]]
[[Category:Penn Abramson Cancer Center]]
[[Category:MSKCC]]
[[Category:Pleural Mesothelioma Treatment]]