Foundation Research Scholar Reports Progress in Discovering Potential Treatments for Peritoneal Spread
About 40% of gastric cancer patients experience “peritoneal” spread, the migration of tumor cells to the lining of the abdomen—a complication that shortens survival. Samuel J. Klempner, M.D., a medical oncologist at Massachusetts General Hospital, is committed to improving the prognosis for these patients, largely by trying to understand why they typically don’t respond well to immunotherapy treatments.
Klempner made headway toward achieving that goal during his three years as a Ben Feinstein Memorial Research Scholar, during which he received $300,000 in funding from the Gastric Cancer Foundation and the American Gastroenterology Association (AGA). With momentum from that grant, which ended in 2023, he and his colleagues have since raised additional funding to pursue novel therapeutic strategies for patients with peritoneal spread.
During his time as a Research Scholar, Klempner and his colleagues profiled more than 600,000 cells from the abdominal fluid of 23 gastric cancer patients. The cells taken from the fluid, which is known as the ascites, included tumor and immune cells.
Klempner and his colleagues are now taking their key findings from that research and launching new studies aimed at discovering novel therapies for peritoneal spread. They have also expanded their dataset to include information from 100 patient samples.
In studying ascites from patients, Klempner’s team discovered high levels of several cytokines, or proteins, that suppress the immune response to cancer. They include IL-6 and IL-8. Klempner is now partnering with another lab at MGH to assess whether combining anti-IL6 and anti-IL8 drugs with immunotherapy treatments might boost the immune system’s ability to kill cancer cells in ascites.
Klempner’s team also feel that they may have identified a novel subgroup of an immune cell population cell that seems to exist only in the peritoneum and pleural cavities. They’re now studying the function of this immune population and the effects of various drug combinations.
Early results from cell studies “point to the idea that you could potentially overcome or remodel the immune suppression that exists in the peritoneum by combining things like IL-6 inhibitors with other immunotherapies,” Klempner said. His goal is to have a combination treatment ready for clinical trials within two to three years if ongoing preclinical work looks promising.
To continue the research into gastric ascites and peritoneal-directed therapies. Klempner’s lab received a Footbridge Bridge Project Grant from the Koch Institute for Integrative Cancer Research at MIT, worth $200,000 per team, and an additional Gastric Cancer Foundation award led by Chloe Villani, Ph.D., a close collaborator on the work.
Klempner is grateful to GCF and AGA for providing vital funding he needed to get his project off the ground. “To find a grant mechanism that’s willing to support high-risk projects is not easy. GCF and AGA were willing to take a shot on something that was plausible but had only a limited amount of preliminary data,” he said. “That was absolutely the foundation of taking this from an idea to what we have now, which is new collaborations and funded grants.”
