The University of Alabama at Birmingham (UniAlB) and two partner institutions received a European patent for their novel approach to fighting cancer (lat. Carcinoma), an approach that is led by the UAB spinoff biopharmaceutical company Incysus Ltd. The company is focused on delivering innovative cellular therapy to treat solid tumor cancers. The European patent is owned by the academic collaborators of Incysus - UAB, Emory University and Children’s Healthcare of Atlanta - and it is licensed exclusively to Incysus for all therapeutic purposes. U.S. Patent applications are pending. The novel cellular therapy is called drug-resistant immunotherapy, or DRI. It is in its preclinical phase, and Incysus is moving toward an investigational new drug application filing with the U.S. Food and Drug Administration to begin tests of safety and efficacy in patients with the brain tumor glioblastoma.
DRI combines two ways to fight cancer - immunotherapy and chemotherapy. While chemotherapy can shrink tumors, immunotherapy uses the body’s own immune system to attack cancer, by stimulating the system or giving the patient additional immune system components. Unfortunately, chemotherapy often destroys the immune cells, and growing cancers can also block an immune response that otherwise would destroy cancer. Tumors also create a tumor microenvironment around the tumor cells that acts as a defensive barrier. By being able to combine chemotherapy and immunotherapy, scientists can use chemotherapy to ablate or modify the tumor microenvironment.
Incysus has supported the UAB laboratory of Lawrence Lamb, Ph.D., professor of medicine, senior scientist in UAB Comprehensive Cancer Center and a scientific co-founder of Incysus, with significant funding as he completes the DRI preclinical phase. Lawrence Lamband H. Trent Spencer, Ph.D., associate professor of pediatrics at Emory University School of Medicine and Incysus scientific co-founder, began the research that eventually led to DRI. Chemotherapy uses potent drugs to kill cancer cells. In their approach, Scientists grow immune cells called gamma delta T cells, and additionally make those T cells resistant to an anticancer drug such as temozolomide. This yields the ability to simultaneously attack a tumor with both immunotherapy - the cancer-killing gamma delta T cells - and chemotherapy. Additionally, it appears that when temozolomide stresses a tumor that has become resistant to temozolomide, an increase in certain surface proteins on the cancer cells act as targets for the gamma delta T cells.
Thus, clinical data from cellular therapies and chimeric antigen receptor T cell (CAR-T) therapies in solid tumor cancers demonstrate that intratumoral heterogeneity and immunosuppression are significant barriers to successful tumor immunity. Invariably, cellular therapies can select for tumors that do not express their targets and immunosuppressive cells such as Tregs can effectively shut down the immune response. Scientists think the future will entail combinations with multiple modes of therapy and this technology uniquely allows to simultaneously combine high-dose chemotherapy with immunotherapy to modify the tumor microenvironment, drive the immune system through a DNA damage response, reduce immunosuppression and create synergies. In combination with checkpoint inhibitors, scientists believe the technology may create a signal that allows directing immune activity against cold, low mutation tumors, where checkpoint inhibitors currently have little activity.