A researcher who has devoted ten years to finding the right target for cancer-fighting CAR-T cells has announced extremely positive results from a Phase 1 clinical trial focused on patients with malignant pleural mesothelioma. The study injected the treatment directly into the chest cavity of 27 patients rather than delivering the medication intravenously, and delivered significantly extended survival times. Dr. Prasad Adusumilli is codirector of the Mesothelioma Program at Memorial Sloan Kettering Cancer Center in New York and lead author of the study, which was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
Study targeted protein found on mesothelioma tumors
The mesothelioma patients involved in the study had all gone through at least three traditional cancer protocols, with most having received a combination of chemotherapy, surgery and radiation therapy. The CAR-T cells used in the study targeted mesothelin, a protein found on many types of cancer, as well as on some healthy cells. Almost all of the patients were dosed with cyclophosphamide, a chemotherapy drug that Dr. Adusumilli believes worked as a pre-conditioning agent. The patients were also dosed with an anti-PD-1 therapy called pembrolizumab in order to further bolster the CAR-T cells after they had killed the cancer cells. This unique combination proved effective. “We noticed that the CAR T cells went to the cancer, killed cells, but get exhausted by PD-1. PD-1 inhibition keeps CAR T cells going,” said Dr Adusumilli.
The results that were seen in the mesothelioma patients were very encouraging. Of the 27 that received the treatment, 63% had either a partial or complete response. The researchers were particularly encouraged that the CAR-T cells were still present in the patients’ pleural fluid for up to 42 weeks after the protocol was administered. The researchers were also pleased that patients experienced only minor negative side effects.
Researchers express optimism about success of novel approach
Speaking on the results of the mesothelioma study, Daniel Abate-Daga, PhD, assistant member of the department of immunology at Moffit Cancer Center and assistant professor in the department of oncological sciences at the University of South Florida, Tampa said, “I was impressed by these results, because mesothelin-targeted trials have been tested before and the results have been a little underwhelming, so the fact we can see a clinical response in this case with minimal toxicity, this is remarkable.” Speaking of his own study, Dr. Adusumilli said, “We are very excited; it’s 10 years of work in my lab finding something to target. We designed the CAR to target tumor and not normal tissue and combined with PD-1. All of these things, previously proven in mice is what we are now able to show in patients.” He went on to explain, “A main reason to be excited about these results is that it opens [up the] possibility of local regional delivery at other sites in the body. I think it’s great that someone was able to show that you can safely and effectively administer cells that can be confined to one region of body and not just migrate in the body.”
If you are a patient who has been diagnosed with malignant mesothelioma and you would like information about CAR-T therapy or how to get involved in a clinical trial, contact the Patient Advocates at Mesothelioma.net at 1-800-692-8608.