Editors' ChoiceCancer Immunotherapy

Virally enhanced immunotherapy

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Sci. Signal.  22 Aug 2017:
Vol. 10, Issue 493, eaao7014
DOI: 10.1126/scisignal.aao7014

A strategy combining immunotherapies with a tumor-targeted virus may be a new treatment option for glioblastoma patients.

Immunotherapy has been effective in some cancers but often requires combination strategies for durable efficacy. Glioblastoma is a challenging disease to treat and to study. Saha et al. tested combination therapies in two mouse models of glioblastoma and found that only a triple combination of an engineered oncolytic virus and two immune checkpoint-blocking antibodies had durable antitumor responses (see also Bell and Ilkow). The authors engineered the oncolytic herpes simplex virus (oHSV) to express the cytokine interleukin-12. This cytokine is toxic when administered systemically, but the virus replicates only in tumor cells; thus, this strategy restricts the production of the cytokine to the tumor. Combining this virus with antibodies against cytotoxic T lymphocyte antigen–4 (CTLA-4) and programmed death receptor–1 (PD-1) elicited durable tumor regression and host survival. The triple combination stimulated tumor infiltration by macrophages and their polarization to the M1 (classically activated) phenotype, increased the ratio of effector T (Teff) cells to regulatory T (Treg) cells, and stimulated tumor cell killing by CD4+ and CD8+ T cells. Treated mice showed antitumor immunity when rechallenged with additional tumor cell implantation. These findings reveal a potentially highly targeted therapy for glioblastoma patients.

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