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Blocking Type 1 Interferon reduces negative side-effects associated with potent immunotherapy

February 25, 2019

Walsh_Scott&Wan_Yonghong
Drs. Scott Walsh and Yonghong Wan (McMaster University)

A group of scientists from the TFRI-funded Canadian Oncolytic Virus Consortium (COVCo) has discovered a new way to reduce negative side-effects associated with a potent form of immunotherapy by blocking the expression of Type 1 Interferon (T1IFN), a key protein of the immune system.  

The findings, which were published in the Journal of Clinical Investigation (February 2019), could be a game-changer for patients with the potential to undergo an experimental immunotherapy treatment that combines adoptive cell therapy with oncolytic virus vaccines.

“We discovered that excessive levels of T1IFN induced during the course of this cancer immunotherapy promoted collateral damage at tissue sites beyond the tumour,” explains Dr. Scott Walsh, a post-doctoral fellow at McMaster University and the paper’s first author. “Taking this into account, we developed a novel cancer immunotherapy to intentionally block T1IFN to prevent damage to normal cells while completely destroying the tumour.”

High toxicity levels remain a major barrier towards making immunotherapy a mainstream cancer therapy. When immunotherapy is administered, the immune system can attack both healthy and unhealthy cells, leading to severe, and possibly life-threatening consequences.

By blocking T1IFN, the team differentiated normal cells from cancerous ones, tricking the immune system to only attack the latter, a discovery that could improve the quality of life of patients being treated with immune therapy.

“Cancer patients and patient advocates want more attention to be paid to the impact of cancer therapeutics on the well-being of the patient. We believe that this study is a start at addressing this concern and, although our study focuses on just one aspect, we hope that it will serve to inspire more similar studies,” says Dr. Walsh.

Study

Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity

Authors

Scott R. Walsh, Donald Bastin, Lan Chen, Andrew Nguyen, Christopher J. Storbeck, Charles Lefebvre, David Stojdl, Jonathan L. Bramson, John C. Bell, and Yonghong Wan

Funding

This work was supported by  The Terry Fox New Frontiers Program Project Grant: Canadian Oncolytic Virus Consortium (COVCo).

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