Greg Delgoffe, who researches cancer immunotherapy at the University of Pittsburgh, recently was awarded the Alliance for Cancer Gene Therapy’s young investor grant. Delgoffe is trying to make immunotherapy, which has been effective fighting cancers of the blood, more effective at fighting solid tumors. We asked him a few questions about his research.
How has immunotherapy advanced progress against hematological cancers?
The last few years have brought a lot of excitement to immunotherapy of hematologic malignancies. Chimeric antigen receptor T cells, which are a patient’s own T cells genetically reprogrammed to recognize tumor targets, have really “changed the game” in blood cancers. These CAR T cells are extraordinarily effective at eliminating cancer cells in the blood. However, scientists and clinicians have not been able to show how effective these types of approaches may be in the treatment of solid tumors.
Why are solid tumors more difficult for immunotherapy to treat?
Solid tumors create what we call a “microenvironment,” which is basically the organ that the cancer cells form that helps them grow and adapt. However, this “environment” is not just full of cancer cells but rather serves as a recruiting station for a distinct constellation of cell types which can disrupt or sabotage the immune response. This can really prevent therapeutic cells or other agents from getting the job done. My lab studies how cancer cells, because they never stop growing and dividing, also act to deplete this microenvironment of nutrients. Immune cells need fuel to carry out their antitumor functions, so solid tumors suppress the immune response, at least in part, by starving the antitumor immune response.
How will your work help advance immunotherapy’s role treating solid tumors, and which types of tumor will you target first?
For the last several years, we have studied the ways that tumor cells starve the immune response, especially what happens to T lymphocytes when they recognize their tumor targets in the microenvironment. What we are trying to do now is correct these metabolic defects. One type of immunotherapy uses therapeutic, tumor specific T cells to treat cancer. We are using genetic engineering approaches to ‘reprogram’ these T cells such that they are metabolically robust, able to survive the dearth conditions of the tumor microenvironment. We are pioneering these studies in mouse models of melanoma, a human cancer which is sensitive to immunotherapeutic approaches but only in a portion of patients. However, we will also be examining how these types of approaches affect the cellular therapy of head and neck, as well as lung cancers.