In the world of cancer treatment, innovation is everything – and one of the most exciting frontiers today is the emergence of CAR T-cell therapy. While this therapy has made headlines for its success in treating blood cancers, many researchers and clinicians now ask: Can this cellular powerhouse be used against tough-to-treat solid tumors like mesothelioma?
What Is CAR T-Cell Therapy?
Chimeric Antigen Receptor (CAR) T-cell therapy is a type of immunotherapy that incorporates elements of gene therapy – known in the scientific community as “cell and gene therapy.” It involves genetically modifying a patient’s T cells, which are cells of the immune system, to recognize and attack cancer cells.
T cells are removed from the patient and modified in a laboratory by receiving a new protein receptor that directs the cells to look for any cells carrying a specific protein. If this protein is unique to cancer cells, then the T cells will become cancer-fighting agents.
These modified cells are returned to the body, where they multiply and target tumor cells with precision.
CAR T-cell therapy has shown dramatic results in blood cancers such as leukemia and lymphoma, with FDA approvals beginning in 2017. There are now seven FDA-approved CAR T-cell therapies for various types of blood cancer.
There have been inspiring stories of survival, such as the stories of Doug Olson and Emily Whitehead. Doug, whose leukemia in 2010 was no longer manageable with chemotherapy, is now 15 years cancer-free and known as the first cancer survivor to receive CAR T-cell therapy.
Emily, who as a young child had exhausted every possible proven treatment option for her leukemia, was close to hospice care at age 6 due to her leukemia. She was the first child to receive CAR T-cell therapy and has been cancer-free for 13 years thanks to the therapy.
Could this therapy be used for solid tumors like mesothelioma and lead to similar stories of survival and hope?
Why Is Mesothelioma So Hard to Treat?
Mesothelioma is a rare and aggressive cancer that usually forms in the lining of the lungs (pleura), lining of the abdomen (peritoneum) or lining of the heart (pericardium). The cancer is caused 100% by asbestos exposure.
Traditional treatment options for mesothelioma like surgery, chemotherapy, and radiation are rarely curative. The prognosis remains poor, with a median survival of around 12 months post-diagnosis.
Treating mesothelioma with CAR T-cell therapy is particularly challenging due to:
- The immunosuppressive tumor microenvironment, which limits T-cell function
- Heterogeneous antigen expression, which means the mesothelioma cells largely express the same proteins found on healthy cells, making it harder to find reliable protein targets
- Difficulty in T-cell penetration and persistence within solid tumors
- The lack of protein targets on the surface of the mesothelioma cells (most unique protein targets are inside of the cells, making it tougher for T cells to identify the cancer cells)
Progress on the Horizon: What’s in the Pipeline?
Despite these challenges, early clinical studies are showing encouraging signs. A key protein target under investigation is mesothelin, a surface protein overexpressed on the surface of mesothelioma cells but limited in normal tissues – making it an ideal candidate for CAR T-cell therapy.
One phase 1 trial from the University of Pennsylvania tested mesothelin-targeted CAR T-cells and showed disease stabilization in several patients without severe toxicity.
Cutting-edge approaches under development include:
- Armored CAR T cells – Engineered to resist immune suppression and secrete cytokines to boost local immune response
- Regional delivery – Administering CAR T cells directly into the pleural cavity to enhance local effects and reduce systemic toxicity
- Combination therapies – Pairing CAR T cells with immune checkpoint inhibitors to prevent T-cell exhaustion and improve persistence
The Road Ahead: Hope Meets Caution
Although CAR T-cell therapy for solid tumors like mesothelioma is still largely experimental, progress is undeniable. Researchers are refining delivery methods, identifying new antigens, and exploring combination strategies that can make this powerful therapy more effective and accessible.
For patients who have exhausted traditional options, clinical trials may offer hope and a path forward. Institutions like the National Institutes of Health, MD Anderson Cancer Center (Houston, TX) and Memorial Sloan Kettering Cancer Center (New York City) are currently enrolling patients in CAR T-cell therapy trials for mesothelioma and other thoracic malignancies.
What Patients Should Know
- Ask your oncologist about CAR T-cell therapy clinical trials specifically for people with mesothelioma.
- Look for trials involving mesothelin-directed CARs or novel delivery methods.
- Stay informed through reliable sources like the American Society of Clinical Oncology (ASCO) and National Cancer Institute (NCI).
Conclusion
CAR T-cell therapy represents one of the most promising innovations in cancer care today. While its use in mesothelioma is still in early stages, the scientific momentum is strong. Each trial and breakthrough brings us closer to answering the question: What’s next, and could it be a cure?
Sources & Author
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- American Cancer Society. (2024). Key Statistics About Mesothelioma.
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- Adusumilli PS, Cherkassky L, Villena-Vargas J, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6(261):261ra151. doi:10.1126/scitranslmed.3010162.
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- ClinicalTrials.gov. CAR T-cell therapy for Mesothelioma.
- Zhang, Y., Wagner, A.K. & Guan, X. Newly approved cancer drugs in China — innovation and clinical benefit. Nat Rev Clin Oncol 20, 135–136 (2023). https://doi.org/10.1038/s41571-023-00728-3.
- Castelletti L, Yeo D, van Zandwijk N, Rasko JEJ. Anti-Mesothelin CAR T cell therapy for malignant mesothelioma. Biomark Res. 2021;9(1):11. Published 2021 Feb 15. doi:10.1186/s40364-021-00264-1.
- Wang Y, Zhao G, Xing S, Wang S, Li N. Breaking through the treatment desert of conventional mesothelin-targeted CAR-T cell therapy for malignant mesothelioma: A glimpse into the future. Pharmacol Res. 2024; 204:107220. doi:10.1016/j.phrs.2024.107220.
- Quach HT, Skovgard MS, Villena-Vargas J, et al. Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy. Cancer Immunol Res. 2023;11(10):1314-1331. doi:10.1158/2326-6066.CIR-22-0840.
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