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Vaccine 'reprograms' pancreatic cancers to respond to immunotherapy
Date:6/17/2014

ty to trigger immune system responses, but there are few options for the other 70 percent of patients who barely or never respond to immunotherapies."

The researchers found that the vaccine created structures called tertiary lymphoid aggregates within the patients' tumor, structures that help regulate immune cell activation and movement. The aggregates, which appeared in 33 of the 39 patients treated with the vaccine, had surprisingly well-organized structures that do not typically appear in these types of tumors naturally, said Zheng, an assistant professor of oncology and surgery at the Johns Hopkins University School of Medicine. "This suggests that there has been significant reprogramming of lymphocyte structures within the tumor."

The aggregates could "really shift the immunologic balance within a tumor, setting up an environment to activate good T cells to fight the cancer, by tamping down Tregs," Jaffee said, "and such T cells would be educated to recognize the cancer proteins in that specific tumor environment."

The vaccine and the resulting lymphoid aggregates boosted the activity of several molecular mechanisms that, like Tregs, inhibit cancer-fighting immune cells. That may sound like a bad thing, but it actually provides many new potential targets within the tumor for immune-modulating drugs, Zheng explained.

The researchers' next study in PDAC patients will test a combination of GVAX and an antibody to PD-1, one of the immune-suppressing molecules that became more active after vaccination. "We think combinations of immune therapies will have the biggest impact," he says.


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Contact: Michelle Potter
mpotter8@jhmi.edu
410-614-2914
Johns Hopkins Medicine
Source:Eurekalert

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