February 14, 2023

Foundation grant could lead to off-the-shelf therapy for cancer

Scientists in the Wayne State University Michael and Marian Ilitch Department of Surgery at the School of Medicine have been awarded a one-year research grant by the Elsa E. Pardee Foundation to develop a new therapy for pancreatic cancer.

Pancreatic cancer is relatively resistant to chemotherapy and typically diagnosed at an advanced stage, thereby precluding surgical resection, and underscoring the need for novel therapies, said principal investigator and Associate Professor of Surgery Ramesh Batchu, Ph.D.

“The utilization of chimeric antigen receptor (CAR) T-cell technology, often called a ‘living drug,’ has ushered in a new era in cancer immunotherapy, especially in hematological malignancies,” he said. “The extraordinary success of this therapy has been attributed to its ability to bypass tumor-imposed immune-inhibitory mechanisms. However, the therapy is ineffective against solid tumors such as pancreatic cancer due to the surrounding tumor microenvironment, or TME, that inhibits T-cell activity. Our goal is the successful application of the CAR T-cell therapy for pancreatic cancer.”

The lab previously demonstrated efficient killing of pancreatic cancer cells in vitro with CAR T-cell therapy targeting cancer-specific mesothelin.

“However, in vivo as mentioned above, the TME inhibits CAR T-cell activity. One of the molecules that is present in the TME and crucial to inhibit T-cell activity is TGF-b. The grant proposal is to nullify the inhibitory effect of TGF-b by gene-editing technology so that the CAR T-cells can kill pancreatic cancer cells in vivo,” Dr. Batchu added. “We hope to bring the CAR T-cell therapy closer to treating solid tumors such as pancreatic cancer. Further, this research will establish the development of off-the-shelf therapy rather than presently practiced patient-specific therapy, which will result in bringing down the costs and making it more affordable to patients.”

Along with Dr. Batchu, the scientific team working on the project include his mentor and co-investigator, Department of Surgery Professor and Chair Donald Weaver, M.D.; WSU master’s student and senior research technician Oksana Gruzdyn; independent investigator Bala Kolli, Ph.D; and lab technician Katia Hermes.

“First and foremost, we are greatly thankful to the trustees of the Elsa U. Pardee Foundation for awarding the grant ‘Mesothelin-Chimeric Antigen Receptor NK-92 Therapy with TGF-beta Inhibition for Efficient Killing of Pancreatic Cancer Cells,’ recognizing the importance of our research work,” Dr. Batchu said.

The project supports the laboratory’s overall objective of designing effective therapeutic cancer vaccines for pancreatic and ovarian cancers.

The Michael and Marian Ilitch Foundation and Department of Surgery provided funds for the research that led to the development of preliminary results submitted as part of the grant application.

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