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- Title
Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy.
- Authors
Bourgeois-Daigneault, Marie-Claude; Roy, Dominic Guy; Aitken, Amelia Sadie; El Sayes, Nader; Martin, Nikolas Tim; Varette, Oliver; Falls, Theresa; St-Germain, Lauren Elizabeth; Pelin, Adrian; Lichty, Brian Dennis; Stojdl, David Francis; Ungerechts, Guy; Diallo, Jean-Simon; Bell, John Cameron
- Abstract
Maraba virus treatment before surgery for triple-negative breast cancer promotes antitumor immunity. Viruses team up with cancer immunotherapy: Immune checkpoint inhibitors have shown great promise for cancer therapy, but they do not treat all cancers, and neither breast nor brain tumors are usually treatable with these drugs. However, Bourgeois-Daigneault et al. discovered a way to address this for breast cancer, and Samson et al. discovered a way to address this for brain tumors. In both cases, the authors found that oncolytic virus treatment given early, before surgical resection, alters the antitumor immune response and potentiates the effects of subsequent treatment with immune checkpoint inhibitors. Although these studies differ in the details of their methods and the immune effects induced by the oncolytic viruses, they indicate the potential of such viruses for enhancing the potential of checkpoint therapy and expanding it to new types of cancer. Triple-negative breast cancer (TNBC) is an aggressive disease for which treatment options are limited and associated with severe toxicities. Immunotherapeutic approaches like immune checkpoint inhibitors (ICIs) are a potential strategy, but clinical trials have demonstrated limited success in this patient cohort. Clinical studies using ICIs have revealed that patients with preexisting anticancer immunity are the most responsive. Given that oncolytic viruses (OVs) induce antitumor immunity, we investigated their use as an ICI-sensitizing approach. Using a therapeutic model that mimics the course of treatment for women with newly diagnosed TNBC, we demonstrate that early OV treatment coupled with surgical resection provides long-term benefits. OV therapy sensitizes otherwise refractory TNBC to immune checkpoint blockade, preventing relapse in most of the treated animals. We suggest that OV therapy in combination with immune checkpoint blockade warrants testing as a neoadjuvant treatment option in the window of opportunity between TNBC diagnosis and surgical resection.
- Subjects
BREAST cancer treatment; CANCER chemotherapy; ONCOLOGY; THERAPEUTICS; RADIOTHERAPY
- Publication
Science Translational Medicine, 2018, Vol 10, Issue 422, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.aao1641