A team at Memorial Sloan Kettering Cancer Center (MSK) led by thoracic surgeon Prasad Adusumilli, MD, has been awarded a distinguished UG3/UH3 grant from the National Cancer Institute (NCI) to advance research and testing of chimeric antigen receptor (CAR) T cell therapy for solid tumors. This funding will support Investigational New Drug (IND) studies, U.S. Food and Drug Administration (FDA) approvals, and a multi-center clinical trial led by MSK. The prestigious grant will advance the translation of recently published high-risk approaches for CAR T cell therapy from the Prasad Adusumilli Lab at MSK.
“Successful completion of this trial and execution of correlative studies will not only advance the field of solid tumor CAR T cell therapy, but also provide novel, effective treatment options to patients with solid tumors whose disease has become resistant to current therapies,” explained Dr. Adusumilli. “We expect that the results can be expanded to the majority of patients with advanced solid tumors.”
While CAR T cell therapy has shown great promise for the treatment of blood cancers, such as leukemia and lymphoma, this type of immunotherapy has so far been much less effective against solid tumors, which account for most cancers. The success of CAR T cell immunotherapy in patients with solid tumors requires effective tumor infiltration, efficient cytotoxicity, and functional persistence. Dr. Adusumilli and team have developed novel approaches to overcome these hurdles:
- Co-opting one of cancer’s own weapons by adding a mutation in a gene called c-KIT to the CAR T cells. When given to animals with human tumors from mesothelioma, other lung, and prostate cancers, these new, tricked-out cells appeared to be more effective than conventional T cells.
- Using tumor-targeted radiation therapy to help CAR T cells penetrate tumors.
- Genetically engineering the CAR T cells to contain a “decoy receptor” that foils cancer cells from blocking the immune cells until they become exhausted.
The clinical trial, which will incorporate all three of these innovations developed at MSK, is built upon the experience of conducting innovative research and trials investigating the use of mesothelin-targeted CAR T cell therapy in patients with mesothelioma or triple-negative breast cancers.
Through this funding opportunity, the NCI intends to accelerate development, innovation, and establishment of adoptive cellular therapy clinical trials for the treatment of adult patients (18 years or older) with solid tumors. Specifically, the UG3 phase of the awards will support preclinical, translational, and IND-enabling studies that lay the groundwork for UH3 early-stage clinical trials testing adoptive immune cell therapies in adults with solid tumors.
This research is supported by the National Cancer Institute of the National Institutes of Health under Award Number 1UG3CA290241-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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