Dr. Mahoney with Bill Bro Photo by © ASCO/Phil McCarten
we’re helping to save lives around the world
Los Angeles, Calif. (PRWEB) October 23, 2014
“We’re pleased to have invested more than $5 million dollars in research-related activities over the past several years,” says Bill Bro, CEO of the Kidney Cancer Association (KCA).
“Just this morning I was directing a family member living in Sweden to treatment resources for her father who lives in Russia. Then, I received an email from someone in the UAE thanking us for helping to find an expert in Singapore. Although our roots are in the USA, we’re helping to save lives around the world,” he added.
KCA collaborates with others in funding research projects aimed at attracting the best and brightest young minds to the field. Recently, working with the Conquer Cancer Foundation, KCA provided funds for a research award to Kathleen M. Mahoney, MD, PhD, at Beth Israel Deaconess Medical Center, for her project “PD‐L1 and a secretory variant in Renal Cell Carcinoma,” mentored by Gordon Freeman, PhD.
Layperson Summary
Tumor expression of PD‐L1 turns off the immune response and lets tumors evade immune attack. Targeting PD‐1 and its ligand PD‐L1 has significantly less toxicity than prior immune therapies, has shown outstanding clinical benefit in Phase I/II clinical trials, and are now in Phase III trials. These include patients with advanced renal cell carcinoma (RCC). Combining blockade of multiple immune checkpoint pathways produces better responses in melanoma. Yet combination therapies also bring higher rates of immune mediated side effects. Therefore it is critical to determine what biomarkers are useful for predicting who will respond to PD‐1 blockade alone and who will require combination therapy. Clinical trials suggested that the PD‐L1 on tumor cells may predict an increased likelihood to respond to PD‐1 therapy. Easy to assay and access biomarkers, such as a biomarker assayable in blood, are particularly needed in this field. PD‐L1 expression on tumors including RCC has been correlated with tumor aggressiveness and poor prognosis. Blood levels of PD‐L1 have been correlated with larger primary tumors and greater necrosis in RCC, but not to advanced disease. The regulation of soluble PD‐L1 has not been determined. While it is reportedly cleaved off the surface, we have found a secreted PD‐L1 (secPD‐L1) splice variant in RCC cells. We hypothesize that secPD‐L1 secreted by RCC tumor cells will be more easily assayed in blood than PD‐L1, and therefore is a better biomarker than biopsy for tumor PD‐L1. We also propose that a subset of tumors solely express this secreted variant, which may explain why some tumors without PD‐L1 surface expression respond to PD‐1 therapies. Our goal is to determine whether secPD‐L1, is a biomarker for PD‐L1 positive RCC. We have evidence that this secPD‐L1 splice variant is a more potent immunosuppressant than the cleaved form of PD‐L1, and may be systemically active. In addition to a better understanding the tumor biology of PD‐L1 and possibly a novel mechanism of systemic immunosuppression by a tumor, this study optimally will develop a biomarker which will help direct treatment decisions for patients with RCC and can be validated in a prospective trial.
“Following completion of her project, Dr. Mahoney will report results to an international group of kidney cancer experts at one of our medical symposia,” Bro says.
KCA was founded in 1990 by a small group of patients, including Eugene P. Schonfeld, Ph.D., and medical doctors in Chicago, Illinois. It is a nonprofit charity incorporated in the State of Illinois. It has also been designated as a tax exempt organization under Section 501(c)(3) of the U.S. Internal Revenue Service code. Donations to the Association are tax deductible.