Prevention of tumor growth of various cancers by T cell engineering

Researchers at Virginia Commonwealth University’s Massey Cancer Center have shown that T cell engineering can prevent the growth of various cancers and prevent them from spreading to other tissues. This study will be published in print tomorrow. Cancer research..

This treatise is based on decades of research by co-author Paul B. Fischer, MD, a member of Massey’s Cancer Biology Research Program, where a protein called IL-24 attacks a variety of things. I found that I would do it. Cancer in several different ways.

In this latest study, Fisher is a colleague, Xiang-Yang (Shawn) Wang, Ph.D., who co-leads Massey’s Development Therapeutic Research Program. In collaboration with, we provided a gene encoding IL-24 called MDA. -7, using for solid tumors T cells..

“I think the beauty of what we’ve been involved with is that it expands the scope of immunotherapy,” said Fisher, a professor and chairman of the Department of Human Molecular Genetics at VCU School of Medicine and director of the VCU Institute. .. Molecular Genetics (VIMM) and Thermaneumer Komann donated the chair of oncology research. “Our approach is less dependent on cancer cells that express something specific to the target.”

After all, this is not the first time T cells have been designed for cancer immunotherapy. FDA-approved chimeric antigen receptor T (CAR-T) cell therapy, designed to destroy cancer cells that express specific surface molecules, has been very successful in treating advanced cancers of the blood and lymphatic system. ..

However, CAR-T can be used for prostate cancer melanomaThis is because the cells that make up these tumors are not all the same, preventing the manipulated T cells from recognizing and attacking them.

Wang and Fisher armed T cells with MDA-7 / IL-24 to broadly target cancer.

“Manipulating T cells to produce MDA-7 / IL-24 can kill cancer cells regardless of the expression of the target molecule, which prevents them from escaping immune attacks.” Wang, who is also a professor of humans and molecules, said. He is the Deputy Director of VCU’s Genetics and VIMM’s Immunology and holds the Harry and Judy Wason Distinguished Professorship at Massey.

At the intracellular level, MDA-7 / IL-24 binds to receptors on the cell surface and directs it to make and release more copies of the MDA-7 / IL-24 protein. If the cells are normal, the protein is simply secreted and no damage occurs. However, when cells are cancerous, MDA-7 / IL-24 causes oxidative stress damage and ultimately cell death not only within the primary tumor but also during its distant metastases. This is the cause of death in 90% of patients.

As a result of this process, the immune system produces memory T cells that can theoretically kill the tumor if it recurs. At the tumor-wide level, IL-24 also blocks the formation of blood vessels and starves tumors of nutrients that are very necessary to maintain unsuppressed growth.

In mice with prostate cancer, melanoma, or other cancer metastases, MDA-7 / IL-24-expressing T cells slowed or stopped cancer progression more than unmodified T cells.

Researchers also found that arming T cells with MDA-7 / IL-24 allows them to survive better and proliferate in the tumor microenvironment (the space immediately surrounding the cancerous mass). did.

Tumor sites are often very hostile to immune cells. We found that MDA-7 / IL-24 helped T cell proliferation and could exceed the number of cancer cells. “

Xiang-Yang (Shawn) Wang, Professor of Human and Molecular Genetics at VCU

In the clinic, this approach involves extracting the patient’s own T cells from a tumor sample, genetically engineering them to express MDA-7 / IL-24, growing millions of cell copies in the lab, and finally. Includes transplantation into patients. Due to federal manufacturing standards, this procedure is generally safe and minimally invasive. CAR-T cells can also be engineered to express MDA-7 / IL-24.

To be most effective, MDA-7 / IL-24T cells may be used in combination with other treatments.

Bringing technology from the bench to the bedside has never been easier, but Fisher is optimistic that many foundations have already been laid.

Clinical trials using various methods of delivering IL-24 are already underway for several cancers. A phase I study using adenovirus (similar to a common cold) to deliver MDA-7 / IL24 to tumors demonstrated approximately 44%. Effectiveness It has proven to be generally non-toxic to multiple forms of cancer.

“I think we have a good start and running ramp that can really accelerate,” Fisher said.

Together, Wang and Fisher recently secured a grant from the National Cancer Institute to optimize their technology for the treatment of solid tumors and cancer metastases in anticipation of future human trials.