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

is antibody is already used for cancer therapy, and it has proved potent in a clinical trial evaluating its combination with another immunotherapy as well.

The researchers noticed that when NDV was injected into a tumor implanted in mice, cancer-killing immune cells flooded into that tumor. "But we also found, to our surprise, that a similar infiltration of activated immune cells occurred in a distant tumor, one in which the virus was never detected," says Zamarin.

The researchers show that NDV infection alerts T cells of the immune system to the presence of cancer cells, which otherwise suppress immune surveillance and attack. Subsequent injection of the anti-CTLA-4 antibody dials up the incipient anti-tumor response so dramatically that it overcomes the tumor's immune suppression and destroys both NDV-exposed tumors and unexposed tumors. And the effect appears to be durable. When the same tumors are reintroduced into treated animals, they are swiftly eliminated.

Combining the two therapeutic strategies, Zamarin explains, overcomes the limitations of each. Oncolytic virotherapy has long been hindered by the immune system's tendency to disable systemically introduced viruses long before they can target tumors. The current study circumvented this problem by injecting NDV directly into the tumor.

Checkpoint blockade, meanwhile, has failed against tumors that suppress immune detection and attack. The researchers found that NDV prompted the cells of such tumors to betray themselves to the immune system when they informed it about the virus. As a consequence, the strategy even made colorectal and prostate tumors that were resistant to immunotherapy susceptible to checkpoint blockade.

The team also found that NDV could be used to boost the effects of an investigationa
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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