# A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab

Source: https://onco.cc/key-papers/paper-adusumilli-cancer-discov/  
OnCo record `paper-adusumilli-cancer-discov` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one idea page, indexed on Europe PMC as PubMed record 34266984 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.

## Summary

Malignant pleural diseases, comprising metastatic lung and breast cancers and malignant pleural mesothelioma (MPM), are aggressive solid tumors with poor therapeutic response. We developed and conducted a first-in-human, phase I study of regionally delivered, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy. Intrapleural administration of 0.3M to 60M CAR T cells/kg in 27 patients (25 with MPM) was safe and well tolerated. CAR T cells were detected in peripheral blood for >100 days in 39% of patients. Following our demonstration that PD-1 blockade enhances CAR T-cell function in mice, 18 patients with MPM also received pembrolizumab safely. Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for ≥6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors. SIGNIFICANCE: Regional delivery of mesothelin-targeted CAR T-cell therapy followed by pembrolizumab administration is feasible, safe, and demonstrates evidence of antitumor efficacy in patients with malignant pleural diseases. Our data support the investigation of combination immunotherapy with CAR T cells and PD-1 blockade agents in solid tumors. See related commentary by Aldea et al., p. 2674. This article is highlighted in the In This Issue feature, p. 2659.

Indexed on Europe PMC as PubMed record 34266984 (DOI 10.1158/2159-8290.cd-21-0407). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Cancer Discovery
- Year: 2021
- DOI: 10.1158/2159-8290.cd-21-0407
- Authors: Adusumilli PS, Zauderer MG, Rivière I, et al.
- What it means: One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Cancer Discov 2021: https://doi.org/10.1158/2159-8290.cd-21-0407
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34266984/
- Europe PMC: https://europepmc.org/article/MED/34266984

## Connected records

- ideas: [Regionally delivered mesothelin CAR-T with PD-1 blockade](https://onco.cc/ideas/idea-mesothelin-car-t-regional/)
- journals: [Cancer Discovery](https://onco.cc/journals/cancer-discovery/)

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