New findings support the administration of a CD40 immune-stimulating drug to early-stage pancreatic cancer patients in advance of surgery. The study, led by researchers in the Abramson Cancer Center (ACC) at the University of Pennsylvania, suggests that pre-treatment CD40 administration could impede progression and later metastasis of cancer.
The team conducted the phase 1b clinical trial at the ACC, Fred Hutchinson Cancer Research Center at the University of Washington, Case Western Reserve University, and Johns Hopkins University. They gathered data from 16 patients who received the CD40 agonist selicrelumab prior to surgery; they also obtained data from a control group of patients who did not receive the treatment. CD40 works by activating antigen-presenting cells, like dendritic cells, to ultimately change the tumor microenvironment from “poor” to “rich”.
The team found that in the patients who received CD40, 82% of their tumors were T-cell enriched, whereas only 37% of untreated tumors were T-cell enriched. Patients receiving CD40 has a median disease-free survival of 13.8 months and median overall survival of 23.4 months, while half of the original group were alive at a median of 20 months after surgery.
The study was presented by Katelyn T. Byrne, PhD, at a plenary session at the American Association for Cancer Research annual meeting. Byrne is an instructor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania.
"Many patients with early-stage disease undergo surgery and adjuvant chemotherapy. But it's often not enough to slow or stop cancer," Byrne said. "Our data support the idea that you can do interventions upfront to activate a targeted immune response at the tumor site -- which was unheard of five years ago for pancreatic cancer -- even before you take it out. This is a first step in building a backbone for immunotherapy interventions in pancreatic cancer.”
The researchers say that their study provides support for further investigations into CD40 therapy combined with other cancer treatments. "We're starting to turn the tide," concludes senior author Robert H. Vonderheide, MD, DPhil, director of the ACC. "This latest study adds to growing evidence that therapies such as CD40 before surgery can trigger an immune response in patients, which is the biggest hurdle we've faced. We're excited to see how the next generation of CD40 trials will take us even closer to better treatments."
Sources: University of Pennsylvania, Science Daily