Intratumor Rotavirus Therapy Has Potential to Overcome Immunotherapy Resistance

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this pre-In this model, researchers infected various tumor cell lines with anti-rotavirus vaccines confirmed to be PRR agonists.
this pre-In this model, researchers infected various tumor cell lines with anti-rotavirus vaccines confirmed to be PRR agonists.

A rotavirus vaccine may help to overcome resistance to immune checkpoint inhibitors used in patients with cancer, according to findings being presented at the 2018 American Association for Cancer Research Annual Meeting in Chicago, Illinois.1

Relatively very few patients have objective responses with immunotherapies including as PD-1 and CTLA-4 inhibitors. Pattern recognition receptors (PRR) are, however, recognized as a potential means for increasing tumor cell immunogenicity and overcoming treatment resistance.

For this pre-clinical model, researchers infected various tumor cell lines with anti-rotavirus vaccines confirmed to be PRR agonists.

In vitro results showed that the rotavirus vaccine not only stimulated PRRs, but also had oncolytic properties: there was an increase in immunogenic cell death in cancer cells with no cytotoxic effects in healthy primary fibroblasts. Similar results were seen in vivo in NSG mice: intratumoral (IT) rotavirus therapy yielded immune-mediated anti-tumor effects.

In immunocompetent murine models of neuroblastoma and lymphoma, IT rotavirus therapy demonstrated that it can overcome immune checkpoint inhibitor resistance — particularly to anti-CTLA-4 therapies — by modifying tumor immune infiltrates and immune activation pathways. An increase of myeloid-infiltrating cells with upregulated levels of CD86 in the tumor microenvironment, as well as an upregulation of the T-cell activation markers OX40/CD137, was observed.

The authors concluded that “in situ immunization strategies with IT attenuated rotavirus can be implemented quickly in the clinic including in pediatric cancers. IT priming of the anti-tumor immunity with oncolytic and immunostimulatory rotavirus vaccines could be a feasible strategy to overcome resistance to anti-PD-1/anti-CTLA-4 therapy in patients with cancer.”

Reference

Shekarian T, Depil S, Jallas AC, et al. Immunostimulatory and oncolytic properties of rotavirus can overcome resistance to immune checkpoint blockade therapy. Oral presentation at: 2018 American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago, IL.

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