Research ArticleCancer Immunotherapy

Localized Oncolytic Virotherapy Overcomes Systemic Tumor Resistance to Immune Checkpoint Blockade Immunotherapy

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Science Translational Medicine  05 Mar 2014:
Vol. 6, Issue 226, pp. 226ra32
DOI: 10.1126/scitranslmed.3008095

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Immune Cells and a Virus Teaming Up to Fight Cancer

Immunotherapy, or harnessing the patient’s own immune system to help fight cancer, is becoming increasingly popular as researchers discover newer and more successful approaches focused on different aspects of the immune system. Two of these approaches include oncolytic viruses and therapies that block immune checkpoints and thus stimulate the antitumor activity of T cells. One virus that is known to have oncolytic activity is Newcastle disease virus (NDV), an avian virus that is not pathogenic in humans. Although previous studies have successfully demonstrated the antitumor effects of NDV, these were thought to require direct injection of this virus into every tumor, thus greatly limiting its effectiveness against metastatic disease.

Now, Zamarin and coauthors used mouse models of cancer with multiple tumor sites to demonstrate that NDV can be used even in the setting of distant spread of disease. Although the virus had to be injected into a tumor to have any effect, the subsequent tumor killing was not limited to the injected tumor. Additional masses that were distant in space and time, such as tumors implanted at different body sites and at later time points, were targeted by the immune system in animals that had been treated with NDV injection into the primary tumor. This immunostimulatory effect of NDV was particularly pronounced when the virotherapy was combined with immune checkpoint blockade by an anti–CTLA-4 antibody.

The current study was performed in mice bearing tumors derived from established cell lines, and the findings will need to be confirmed in the setting of spontaneously arising metastatic tumors. Nevertheless, the results of this work raise the tantalizing possibility that two therapies known to be safe for human use could be combined and work with the immune system to eradicate tumors throughout the body.