Cellular Immunotherapy and Locoregional Administration of CAR T-Cells in Malignant Pleural Mesothelioma

Our plain-English summary of Cellular Immunotherapy and Locoregional Administration of CAR T-Cells in Malignant Pleural Mesothelioma, by R.A. Belderbos, H. Vroman, J.G.J.V. Aerts (Frontiers in Oncology, 2020).

The study

• Authors: R.A. Belderbos, H. Vroman, J.G.J.V. Aerts
• Journal: Frontiers in Oncology
• Published: 2020;10:777
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a treatment recalcitrant tumor with a poor overall survival (OS). Current approved treatment consists of first line chemotherapy that only modestly increases OS, illustrating the desperate need for other treatment options in MPM. Unfortunately, clinical studies that investigate the effectivity of checkpoint inhibitor (CI) treatment failed to improve clinical outcome over current applied therapies. In general, MPM is characterized as an immunological cold tumor with low T-cell infiltration, which could explain the disappointing results of clinical trials investigating CI treatment in MPM. Currently, many other therapeutic approaches, such as cellular therapies and cancer vaccines are investigated that could induce a tumor-specific immune response and increase of the number of tumor-infiltrating lymphocytes. In this review we will discuss these novel treatment approaches for MPM.

Copyright © 2020 Belderbos, Vroman and Aerts.

In plain English

This mini review described experimental immune-based treatments for malignant pleural mesothelioma (MPM): cancer vaccines, dendritic cell (DC) therapy and CAR T-cell therapy. It did not study asbestos exposure. It summarised published and ongoing trials rather than reporting a new study. In the trials it described, a vaccine called CRS-207 given with chemotherapy produced 1 complete and 19 partial responses among 35 evaluable patients. The authors said its median survival of 14.7 months was comparable to standard chemotherapy. In a phase I trial of ten patients given DC therapy made with their own tumor material, three had partial responses. Among nine patients at the authors' center who had DC therapy followed by checkpoint inhibitors, three had partial responses. One trial gave CAR T-cells into the pleural space of 21 patients with malignant pleural disease. Of these, 19 had MPM, and 13 of the 19 later also received the checkpoint inhibitor pembrolizumab. Two patients had complete and five had partial responses as best response. The authors concluded that more research is needed to investigate and compare these therapies, and that checkpoint inhibitors could enhance them.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Mini review (narrative review of clinical trials and some animal studies)
• Who was studied: No patients were studied directly. The review covered completed and ongoing clinical trials, and some mouse studies, of immune-based treatments in malignant pleural mesothelioma (MPM).
• Exposure: Not asbestos exposure. The subject was treatments for MPM: cancer vaccines (WT-1 peptide vaccine Galinpepimut-S, CRS-207), dendritic cell therapy, and CAR T-cell therapy, including CAR T-cells given into the pleural space.
• Main results:
  • Reviewed phase Ib trial of CRS-207 with pemetrexed/cisplatin in treatment-naive MPM patients: disease control rate 89%, with 1 complete response and 19 partial responses in 35 evaluable patients. Median overall survival was 14.7 months, which the authors called comparable to standard chemotherapy.
  • Reviewed randomized phase II trial of Galinpepimut-S versus adjuvants alone: the trial was closed after 41 patients. The increase in median survival for treated patients was not statistically significant.
  • Reviewed phase I trial of DC therapy loaded with the patients' own tumor lysate in ten MPM patients: 3 partial responses, 1 stable disease and 6 progressive disease. Median survival from diagnosis was 19 months.
  • Reviewed phase I dose-escalation trial of DC therapy loaded with allogeneic tumor lysate (MesoPher): 2 of 9 MPM patients had a partial response.
  • Nine MPM patients treated with DC therapy at the authors' center and then given checkpoint inhibitors: 3 partial responses and 5 stable disease. Median survival was 17.5 months from the start of checkpoint inhibitor treatment.
  • Reviewed phase I trial of 4-1BB mesothelin CAR T-cells in patients with MPM, ovarian carcinoma and pancreatic ductal carcinoma: no radiological responses, and 11 of 15 patients had stable disease as best overall response.
  • Reviewed trial of intrapleural CD28 mesothelin CAR T-cells in 21 patients with malignant pleural disease. Of these, 19 had MPM, and 13 of the 19 were subsequently treated with pembrolizumab. As best overall response, 2 had a complete response, 5 a partial response and 4 stable disease.
• The authors' conclusion: The authors concluded that additional research is needed to investigate and compare the effectiveness of cancer vaccines and cellular therapies in MPM. They also concluded that checkpoint inhibitors could enhance both kinds of treatment by reinvigorating tumor-infiltrating T-cells.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Overall Survival, Chemotherapy, checkpoint inhibitors, Clinical Trial, Tumor-Infiltrating Lymphocytes.

Related studies

• T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma — H. Vroman, G. Balzaretti, et al. (2020)
• Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients — L.A. Lievense, K. Bezemer, et al. (2017)
• Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy — L. Noordam, M.E.H. Kaijen, et al. (2018)
• Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer — F.R. van 't Land, M. Willemsen, et al. (2024)
• Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial — M.V. Dietz, K.L.A. Quintelier, et al. (2023)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)

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