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Going viral to target tumors
Date:3/5/2014

March 5, 2014, New York, NY A Ludwig Cancer Research study suggests that the clinical efficacy of checkpoint blockade, a powerful new strategy to harness the immune response to treat cancers, might be dramatically improved if combined with oncolytic virotherapy, an investigational intervention that employs viruses to destroy tumors.

Published today in the journal Science Translational Medicine, the study evaluated a combination therapy in which the Newcastle disease virus (NDV), a bird virus not ordinarily harmful to humans, is injected directly into one of two melanoma tumors implanted in mice, followed by an antibody that essentially releases the brakes on the immune response. The researchers report that the combination induced a potent and systemically effective anti-tumor immune response that destroyed the non-infected tumor as well. Even tumor types that have hitherto proved resistant to checkpoint blockade and other immunotherapeutic strategies were susceptible to this combined therapy.

"Many patients have benefited from cancer immunotherapies," says Dmitriy Zamarin, a member of Ludwig's Collaborative Laboratory at Memorial Sloan Kettering Cancer Center (MSK) and lead author of the study together with James Allison of the MD Anderson Cancer Center in Houston, and Jedd Wolchok, Director of the Ludwig Collaborative Laboratory at MSK. "But they have not been effective for all patients, or against all cancer types, since most cancers can potently suppress immune responses. We want to extend the benefits of immunotherapies to more patients and optimize their use against a larger variety of cancers."

Zamarin and his colleagues found that an inflammatory immune response induced in the tumor by NDV primarily accounts for the efficacy of the therapy. The checkpoint blockade antibody used in this study binds CTLA-4, a molecule found on immune cells that acts like a brake (or "checkpoint") on the immune response. A version of th
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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