Mouse model shows CD40-activated macrophages, not T cells, aid depletion of the tumor stroma

Friday, March 25, 2011 (Last Updated: 03/28/2011)

FRIDAY, March 25 (HealthDay News) -- A novel immune therapy using CD40 agonist antibodies to attack the stroma surrounding pancreatic tumors appears to show efficacy in mice and humans, according to a study published online March 25 in Science.

Gregory L. Beatty, M.D., Ph.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues investigated whether systemic activation of CD40 with an agonist CD40 antibody can reverse tumor-induced immune suppression in both mice and humans. A small cohort of 21 patients with surgically incurable pancreatic ductal adenocarcinoma (PDA) was treated with standard gemcitabine as well as an agonist CD40 antibody. Mouse models were used concurrently to understand the human response to the immune therapy.

The researchers found that some patients experienced tumor regression and a loss of tumor metabolic activity; however, all the patients eventually relapsed. The treatment effect was reproduced in a genetically engineered mouse model of PDA, where it was observed that the CD40 antibody caused macrophages to rapidly infiltrate the tumor, become tumoricidal, and weaken the tumor stroma. The mouse model also demonstrated that tumor regression required macrophages, but not T cells or gemcitabine.

"Our findings identify a previously unappreciated role for the CD40 pathway in regulating the immune reaction and fibrosis associated with PDA by re-education of tumor-associated macrophages. Mechanistically, CD40 agonists altered tumor stroma and, in both mice and humans, showed efficacy against PDA," the authors write.

Several of the study authors disclosed financial ties to Pfizer Corporation, which partially funded the study.

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Specialties Hematology & Oncology

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