Current Advances in CAR T Cell Therapy for Malignant Mesothelioma

Our plain-English summary of Current Advances in CAR T Cell Therapy for Malignant Mesothelioma, by A. Klampatsa, S.M. Albelda (Journal of Cellular Immunology, 2020).

The study

• Authors: A. Klampatsa, S.M. Albelda
• Journal: Journal of Cellular Immunology
• Published: 2020;2(4):192-200
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a relatively rare malignancy arising in the body's serosal surfaces, with malignant pleural mesothelioma (MPM) being the most common type. It is characterized by local spread within the thorax, poor prognosis and resistance to treatment. The development of various immunotherapeutic options has provided a new way- and hope- in treating cancer patients. Chimeric antigen receptor (CAR) T cell therapy has been proven very successful in treating hematological cancers, like leukemias and lymphomas, and its use is now being tested in solid tumors. CARs that recognize and bind to a specific tumor-associated antigen on the tumor's cell surface, are engineered and transduced into T cells. Interaction of the CAR T cell with the tumor then results in T cell activation and subsequent tumor cell lysis. In this review, we provide a current update on our previous comprehensive study summarizing the CAR T cell preclinical studies and clinical trials in MM, and discuss the future perspectives of CAR T cell therapy in this disease.

In plain English

This review updated the authors' earlier summary of laboratory and clinical research on CAR T cell therapy (patients' own immune cells engineered to attack a target) for malignant mesothelioma, mainly pleural. It described previously reported trials rather than presenting a new one. In a University of Pennsylvania safety trial, no patient developed inflammation of the linings of the lungs, abdomen or heart from the CAR T cell infusion, but no clinical responses were evident. One patient had a serious anaphylactic reaction. A second trial of 15 patients with mesothelioma, ovarian or pancreatic cancer reported a best response of stable disease in 11 of 15. Preliminary conference results from a Memorial Sloan Kettering trial of 27 patients (25 with pleural mesothelioma) reported partial or complete responses in 63% of those who also received cyclophosphamide and at least three pembrolizumab doses; the review does not give that group's size. In a Zurich trial, 2 of 3 pleural mesothelioma patients were alive at a median follow-up of 18 months. The authors concluded that clear success of CAR T cells in any solid tumor had not yet been achieved.

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: narrative review updating the authors' earlier summary of preclinical studies and clinical trials
• Who was studied: published preclinical studies, clinical trials and conference reports of CAR T cell therapy in malignant mesothelioma, chiefly malignant pleural mesothelioma (MPM); several trials also enrolled patients with other cancers
• Exposure: CAR T cell therapy (a treatment, not asbestos exposure). In clinical trials the targets were mesothelin on tumor cells and fibroblast activation protein (FAP) on tumor stromal cells. Other targets (pan-ErbB 'T4', 5T4, CSPG4, MET) were described from preclinical studies.
• Main results:
  • In the first University of Pennsylvania phase I safety trial (NCT01355965), as reported in the review, no patient had 'on target, off tumor' toxicity (pleuritis, peritonitis, pericarditis) from the CAR mesothelin T cell infusion, and there were no evident clinical responses.
  • In that trial, one patient had an immediate serious anaphylactic reaction.
  • A second phase 1 trial (NCT02159716) enrolled 15 patients with mesothelioma, ovarian cancer and pancreatic cancer.
  • In that second trial, the best overall response was stable disease in 11 of the 15 patients.
  • Preliminary results from the Memorial Sloan Kettering trial (NCT02414269) covered 27 patients, 25 of whom had MPM, and were presented at the 2019 ASCO meeting.
  • Among patients in that trial who received cyclophosphamide, CAR T cells and at least 3 doses of pembrolizumab, 63% had a partial or complete response. The number of patients in this subgroup is not given.
  • In the Zurich FAP-targeted CAR T cell trial (NCT01722149), preliminary results presented in 2019 showed that 3 MPM patients tolerated treatment well, and 2 of the 3 were alive at a median follow-up of 18 months.
  • CARs against other tumor targets in MPM were described as still being studied preclinically.
• The authors' conclusion: The authors concluded that clinical trials of CAR T cells in mesothelioma were underway, but that clear success of CAR T cells in any solid tumor had not yet been achieved.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Serosal Surface, Pleural Mesothelioma, Thorax, Prognosis, Clinical Trial.

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