Optimizing the Immune System to Beat Cancer

Newswise — Chimeric antigen receptor (CAR) T-cell therapy amplifies the immune system’s ability to recognize and kill cancer cells. The first CAR T-cell therapy was approved by the Food and Drug Administration (FDA) in 2017. Today, there are 6 FDA-approved CAR-based therapies to treat certain types of leukemia, lymphoma and myeloma, all of which are available at The University of Kansas Cancer Center.

Joseph McGuirk, DO, division director of the cancer center’s Hematologic Malignancies and Cellular Therapeutics program, is a national leader in cellular therapy research and treatment. He is spearheading an effort that will test a novel CAR product created at the cancer center, for the treatment of lymphoma and acute lymphoblastic leukemia. The collaboration includes researchers at the cancer center, Children’s Mercy and the National Cancer Institute (NCI).

Casting a wider net

CAR T-cell therapies are tailor-made for each person. In this approach, T-cells are removed from a patient, equipped with new proteins that allow them to detect cancer, and infused back into the patient. The new proteins – CARs – recognize and attach to specific antigens on the surface of cancer cells. All CAR T-cell therapies currently approved by the FDA target a single antigen. 

One reason CAR T-cell therapy sometimes fails is that the cancer cells may stop making the targeted antigen. This is called antigen loss, and it occurs in an estimated 30-50% of people. To reduce the risk of antigen loss, Dr. McGuirk and Sunil Abhyankar, MD, professor in the Department of Hematologic Malignancies and Cellular Therapeutics, are casting a wider net. Their goal is to create a CAR T-cell therapy that targets not 1, but 3 types of antigens: CD19, CD20 and CD22. 

“Cancer may evade CAR T-cells if it’s not expressing the same targeted antigen. We believe this combination approach could expand the CAR’s ability to effectively target and treat some types of cancer,” Dr. McGuirk says. “If CD19 is not expressed, for example, we have a chance of targeting it with the other two molecules.”

Creating CAR T-cells in-house

Manufacturing CAR T-cells is no small feat. Each treatment must be made for the individual patient; it is a sophisticated and time-sensitive process. Once T cells are drawn from study participants, they will be shipped to our cancer center researchers and modified in a state-of-the-art environment.

The University of Kansas Medical Center’s Midwest Stem Cell Therapy Center contains a Good Manufacturing Practices (GMP) laboratory that meets rigorous quality control regulations set by the FDA. Dr. Abhyankar leads the Midwest Stem Cell Therapy Center and is a key member of the team leading the study. 

Once modified and expanded in the GMP laboratory, the cells will be reinfused into study participants at one of 3 treatment sites: our cancer center, Children’s Mercy and NCI. 

“Creating CAR T-cells onsite requires a robust infrastructure and highly specialized experts. This type of manufacturing is found almost exclusively in NCI-designated comprehensive cancer centers like ours,” Dr. McGuirk says. “A mom-and-pop shop couldn’t pull this off.”

The tip of the iceberg

Over the last few years, Dr. McGuirk and his team have published multiple manuscripts about cellular therapies in prestigious journals like the New England Journal of Medicine, The Lancet, Journal of Clinical Oncology and Nature Medicine. In addition, the cancer center is conducting more than 20 active CAR T-cell clinical trials. But it’s just the tip of the iceberg according to Dr. McGuirk. Researchers at the cancer center are looking beyond CAR T-cells to develop new cell-based therapies.

Like CAR T-cell therapy, T-cell receptor (TCR) therapy involves engineered cells to treat cancer. CARs use receptors to find antigens they’re engineered to see on the cell surface. TCRs, on the other hand, use their natural receptors to recognize antigens inside tumor cells. Researchers at the cancer center are studying the use of TCRs in blood cancers and solid tumors.

Another experimental cell therapy to treat solid tumors involves the use of tumor infiltrating lymphocytes (TILs). Lymphocytes are part of the immune system, and they penetrate cancers when detected. Gary Doolittle, MD, professor in the Department of Medical Oncology and medical director of Masonic Cancer Alliance, is leading an effort studying the use of TILs in people with melanoma. Surgeons surgically remove the melanoma tumor and send it to the laboratory, where its T cells are extracted, grown and infused back into the patient. Because TILs come directly from the patient’s tumor, they already recognize many targets on the cancer cells. This could enable them to kill cancer cells more effectively. 

“The studies supporting the use of TIL therapy in melanoma are really exciting. This opens up a very different therapeutic avenue to possibly control melanoma when standard therapies fail,” Dr. Doolittle says.

These efforts, and more, are part of the cancer center’s efforts to expand the use of cell therapy, while making it more effective and less toxic. 

 “The cancer center has put in place a number of tools and facilities that are helping our researchers improve the cancer treatment landscape,” Dr. McGuirk says. “As a result, we can offer the latest cell-based therapies to our patients.”