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Review
. 2016 Jul:9:31-36.
doi: 10.1016/j.ebiom.2016.06.046. Epub 2016 Jul 2.

Oncolytic Viruses: Therapeutics With an Identity Crisis

Caroline J Breitbach  1 , Brian D Lichty  2 , John C Bell  3
Affiliations
Review

Oncolytic Viruses: Therapeutics With an Identity Crisis

Caroline J Breitbach et al. EBioMedicine. 2016 Jul.

Abstract

Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.

Keywords: Immune checkpoint inhibitors; In situ vaccine; Oncolytic immunotherapy; Oncolytic virus.

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Figures

Fig. 1
Fig. 1
Oncolytic viruses sensitize tumours to immune checkpoint inhibitors. By ‘releasing the brakes’ on T cells, immune checkpoint inhibitors rely on a pre-existing anti-tumour immune response for clinical activity. OV infection of the tumour bed releases tumour antigens and results in T cell recruitment to tumours. These T cells are then ‘un-inhibited’ by immune checkpoint inhibitor antibodies.
Fig. 2
Fig. 2
Mechanism of MG1 immune boost. The oncolytic virus MG1 expressing a tumour associated antigen transiently infects B cells in the splenic follicle. Antigens expressed on these cells are transferred to follicular dendritic cells that present antigen to TCM cells. The splenic follicles are immune privileged sites as TEFF cells can not enter. Therefore, follicular dendritic cells are protected from TEFF cell killing, a negative feedback loop (Bridle et al., 2016). This provides a mechanism for the large anti-tumour immune responses observed following treatment with MG1 expressing a tumour antigen (Pol et al., 2014).
See this image and copyright information in PMC

References

    1. Adair R.A., Roulstone V., Scott K.J., Morgan R., Nuovo G.J., Fuller M., Beirne D., West E.J., Jennings V.A., Rose A., Kyula J., Fraser S., Dave R., Anthoney D.A., Merrick A., Prestwich R., Aldouri A., Donnelly O., Pandha H., Coffey M., Selby P., Vile R., Toogood G., Harrington K., Melcher A.A. Cell carriage, delivery, and selective replication of an oncolytic virus in tumor in patients. Sci. Transl. Med. 2012;4 (138ra77) - PMC - PubMed
    1. Andtbacka R.H., Kaufman H.L., Collichio F., Amatruda T., Senzer N., Chesney J., Delman K.A., Spitler L.E., Puzanov I., Agarwala S.S., Milhem M., Cranmer L., Curti B., Lewis K., Ross M., Guthrie T., Linette G.P., Daniels G.A., Harrington K., Middleton M.R., Miller W.H., JR., Zager J.S., Ye Y., Yao B., Li A., Doleman S., Vanderwalde A., Gansert J., Coffin R.S. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 2015;33:2780–2788. - PubMed
    1. Arulanandam R., Batenchuk C., Angarita F.A., Ottolino-Perry K., Cousineau S., Mottashed A., Burgess E., Falls T.J., De Silva N., Tsang J., Howe G.A., Bourgeois-Daigneault M.C., Conrad D.P., Daneshmand M., Breitbach C.J., Kirn D.H., Raptis L., Sad S., Atkins H., Huh M.S., Diallo J.S., Lichty B.D., Ilkow C.S., Le Boeuf F., Addison C.L., Mccart J.A., Bell J.C. VEGF-mediated induction of PRD1-BF1/Blimp1 expression sensitizes tumor vasculature to oncolytic virus infection. Cancer Cell. 2015;28:210–224. - PubMed
    1. Breitbach C.J., Paterson J.M., Lemay C.G., Falls T.J., Mcguire A., Parato K.A., Stojdl D.F., Daneshmand M., Speth K., Kirn D., Mccart J.A., Atkins H., Bell J.C. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol. Ther. 2007;15:1686–1693. - PubMed
    1. Breitbach C.J., Burke J., Jonker D., Stephenson J., Haas A.R., Chow L.Q., Nieva J., Hwang T.H., Moon A., Patt R., Pelusio A., Le Boeuf F., Burns J., Evgin L., De Silva N., Cvancic S., Robertson T., Je J.E., Lee Y.S., Parato K., Diallo J.S., Fenster A., Daneshmand M., Bell J.C., Kirn D.H. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. 2011;477:99–102. - PubMed

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