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Vivek Verma, PhD, Assistant Professor and section leader of the Immunology, Cancer Immunotherapy and Immune Metabolism at The Hormel Institute, University of Minnesota, is the recipient of a two-year, $200,000 grant from the Cancer Research Institute. The highly competitive Cancer Research Institute’s Clinical Laboratory Integration Program (CRI CLIP) grant will support Verma’s lab efforts to improve mitochondrial metabolism in immune cells to make immune checkpoint-based immunotherapy more effective in treating solid tumors.

The Verma Lab’s study is a first of its kind in that it will try a combination of mitochondria-targeted and immune checkpoint-targeted therapy in melanoma. Melanoma, the most severe type of skin cancer, arises in melanocytes, the cells that produce melanin in the skin, hair, and eyes. 

Immunotherapy uses a patient’s own immune system to fight cancer. Immune checkpoint inhibitor (ICI) therapy, a type of immunotherapy, helps the body’s immune cells identify and attack cancer cells more effectively.

But immunotherapy is currently more effective for certain types of cancers than for others. There are two main classifications of cancer: solid and liquid. Immunotherapy is remarkably effective in treating liquid cancers, such as leukemias.

However, for now, immunotherapy has a limited efficacy rate of just 20% to 30% when treating patients with solid tumors. ICI therapy options such as anti-PD1 are promising treatment strategies for patients with advanced stages of melanoma—but even in best-case scenarios, approximately only half of patients respond to treatment. 

One of the primary challenges in using immunotherapy to treat solid tumors is that immune cells in solid tumors tend to have dysfunctional mitochondria. Since mitochondria are responsible for providing energy for a cell, this leads to immune cells becoming exhausted by the time they enter the tumor bed, which leaves them unable to effectively fight off cancer cells.

Through the current CRI-sponsored project, Dr. Verma intends to improve the therapy response in melanoma by preventing mitochondrial exhaustion in immune cells.

 “There are many therapeutic avenues that are being tried in clinics against solid tumors that include immune checkpoint inhibitors, adoptive cell therapy and chimeric antigen receptor (CAR) cell therapies, which are all susceptible to failure owing to exhaustion in

immune cells,” Verma said. “The present study is extremely important in advancing our understanding of the exhaustion mechanisms, and in developing strategies to reverse this exhaustion.”

Another important vision of this funding mechanism is to encourage bench to bedside studies, where results from research in the laboratory are taken into the clinic to directly benefit patients.

To date, no clinically relevant strategies are yet available to boost mitochondrial metabolism. As a CRI CLIP Investigator, the Verma Lab seeks to change this by developing clinically relevant mitochondria-directed pharmacological treatment strategies that could be used to help immune cells last longer to make cell therapy more effective.

More information about the CRI CLIP grant and \Verma’s project are available on the CRI website: www.cancerresearch.org/cri-funded-scientists/vivek-verma-phd.