NFCR Basic Research in Action: Immunotherapy

The immune system is the body’s defense against disease as it recognizes and destroys any foreign material that could cause harm. In some instances, the immune system can recognize cancer cells as abnormal and kill them; in others, the cancer evades the immune system wreaking havoc in our bodies.

In recent years, some of the most promising advances in cancer research involve immunotherapies – treatments that use the immune system to fight diseases like cancer. By finding new ways to help the immune system recognize cancer cells –  specifically in solid tumors, and strengthen its response to destroy them, researchers are looking for long-lasting solutions to cure cancer.

The new immunotherapy called checkpoint inhibitors—that unleashes the brake on our immune system to recognize and fight cancer cells—is successful in some cancers but not in treating the aggressive brain cancer, glioblastoma or GBM.  Dr. Rakesh Jain’s research focuses on combining anti-angiogenic treatment with the immunotherapy of immune checkpoint inhibitors to treat GBM effectively. His lab has previously shown and is renowned for the concept that a disturbed balance of blood vessel growth factors in tumors results in abnormal tumor vessels that cause a lack of oxygen and immunosuppression. If this research is successful, the results will directly inform the design of clinical trials testing their novel treatment strategies to overcome resistance to checkpoint inhibitors.

In collaboration, NFCR-funded scientists, Dr. Paul Schimmel and Dr. Xiang-Lei Yang discovered that the vital protein synthesis enzyme, SerRS, has critical anti-cancer properties. In complex tumor models of triple negative breast cancer, not only does SerRS shut down angiogenesis (blood vessel formation), it may activate the immune system to suppress cancer progression and metastasis.  This research may lead to a novel treatment for breast, brain, rectal, esophageal, kidney lung and thyroid cancer.

Dr. Wei Zhang’s research concerns different aspects of immunotherapy to advance its use for precision medicine. Predictive biomarkers are needed to determine in advance patients with the most potential to benefit from the type of immunotherapy called checkpoint inhibitors. His team uses bioinformatics analysis to perform an in-depth characterization of immune cell subsets in patient’s blood. They have observed a repertoire of immune cell dynamics and they hope to reveal useful biomarkers from a blood sample to help predict patient responses.

Another focus concerns the health disparity in non-small cell lung cancer (NSCLC). African Americans (AA) have a higher incidence in NSCLC and worse outcome relative to Caucasian Americans (CA). Dr. Zhang’s team observed AA lung cancer patients had higher immunosuppressive system components that would support worse outcomes for patients. However, the reduced levels of one population of immune system T cells (fighter cells of our immune system) may actually favor a heightened response to immunotherapy ‘checkpoint inhibitor’ treatment in AA patients.

They are developing the largest dataset of single-cell RNA sequencing (to examine the immune cell components) for AA patients with NSCLC. They will make it available to the cancer research field and hope the dataset may contribute to a reduction in cancer health disparities in the near future.

Dr. Laurence Cooper, a pediatric oncologist and scientist who received NFCR support for 11 years, is a pioneer in developing adoptive immunotherapy. This novel approach called ‘CAR-T Cell therapy’ first collects cancer patients’ T cells (our white blood cells of our immune system) and engineers the cells in the laboratory to express an antenna-like molecule called CAR (chimeric antigen receptor) that recognized antigens (proteins) on cancer cells. Once infused back to patients, the CAR-T cells have enhanced cancer-fighting capacity and stimulate patient’s immune system. His research has helped advance the new promising immunotherapies using CAR T cells for leukemia and lymphoma patients.

Dr. Paul Fisher discovered a powerful cytokine, IL/24, or immune system modulator that destabilizes both primary and metastatic cancer cells resulting in direct killing or indirect toxicity through activation of the immune system and inhibition of angiogenesis. IL/24 gene therapy is effective against many types of solid tumors and he has developed innovative ways to deliver IL/24 gene therapy to the body including adoptive cell therapy. Dr. Fisher and Dr. Web Cavenee are first advancing IL/24 gene therapy for the deadly brain cancer, glioblastoma or GBM.