CRI has a long history of supporting research that has improved the treatment of kidney cancer, from research on IL-2 and interferon to current treatment approaches using checkpoint blockade. In 1978, Jordan Gutterman, M.D., received funding from CRI to conduct a clinical trial of interferon-alpha in human patients. The study showed that kidney cancer is sensitive to interferon and paved the way for the FDA approval of this treatment.
In 1993, CRI researchers Drew Pardoll, M.D., Ph.D., Glenn Dranoff, M.D., Elizabeth Jaffee, M.D., Hyam Levitsky, M.D., and colleagues conducted preclinical studies showing that a vaccine composed of tumor cells irradiated and genetically modified to produce immune system growth factor GM-CSF (granulocyte macrophage colony-stimulating factor) could induce potent, specific, and long-lasting anti-tumor immunity in multiple mouse tumor models. Based on these preclinical findings, CRI provided funding for a phase I clinical trial to test the vaccine in patients with metastatic renal cell carcinoma. This work led to the therapeutic cancer vaccine GVAX.
In 1999, CRI researchers including Neil Bander, M.D., Dirk Jäger, M.D., Elke Jäger, M.D., Alexander Knuth, M.D., and Lloyd J. Old, M.D., used SEREX technology to identify tumor-associated antigens in patients with renal cell carcinoma. This work provided an important foundation for the idea that renal cancer is immunogenic—able to be recognized by the immune system.
In 2010, CRI researchers Drew Pardoll, M.D., Ph.D., Susan Topalian, M.D., and colleagues completed a phase I study showing that a PD-1-specific monoclonal antibody induces frequent tumor regressions in patients with advanced melanoma, renal cancer, lung cancer, and colon cancer with very low rates of toxicity. This study helped establish that PD-1 blockade is a promising new therapy for multiple types of cancers, including ones for which currently approved therapies are not effective.
In 2012, Jeffrey Rathmell, Ph.D., of Vanderbilt University, was awarded a Clinic and Laboratory Integration Program (CLIP) grant from CRI to study the metabolism of kidney cancer cells and the immune cells that surround them. Rathmell and colleagues have shown that T cells that mediate anti-tumor immunity are highly dependent on glucose. If access to glucose is limited, T cells fail to function and instead can become regulatory T cells that suppress immunity. But kidney cancer needs glucose too, and this shared need for glucose fosters competition for nutrients within the tumor that may suppress anti-tumor immunity. These studies may provide a new way to augment anti-tumor immunity by manipulating glucose metabolism. His work also suggests that therapies designed to block immune checkpoints, such as anti-PD-1 antibodies, may act in part by shifting this metabolic competition back in favor of immune cells.