Research ArticleCancer Immunotherapy

Oncolytic and Immunotherapeutic Vaccinia Induces Antibody-Mediated Complement-Dependent Cancer Cell Lysis in Humans

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Science Translational Medicine  15 May 2013:
Vol. 5, Issue 185, pp. 185ra63
DOI: 10.1126/scitranslmed.3005361

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The Enemy of My Enemy Is My Friend: Virotherapy for Cancer

Oncolytic viruses, which can kill cancer cells directly and by stimulating the patient’s immune system, have some clear advantages over other immune approaches to cancer treatment. They do not induce autoimmunity, they do not have to be custom-made for each patient, and they are not specific to tumors that express a particular antigen. Previous works with these viruses have shown promising results, and some of them are now in clinical trials. However, the steps by which these viruses exert their effects against the cancer cells in animals and humans are not yet fully understood. Now, the work by Kim et al. uncovers some of the mechanism for the action of Pexa-Vec, a vaccinia virus–derived oncolytic vaccine, which is already being tested in patients with multiple types of advanced cancers.

In a rabbit model of squamous cell carcinoma, the authors demonstrated the induction of antibody-mediated complement-dependent cytotoxicity (CDC) after treatment with Pexa-Vec. The resulting antitumor activity could be transferred from one rabbit to another by transferring serum, even long after the virus was administered and then cleared from the blood, providing additional evidence for the role of antibodies. Serum from human patients treated with Pexa-Vec also induced CDC against cancer cells, primarily against cancer of the same type. For example, serum from a renal cancer patient treated with the virus was most effective at triggering CDC against renal cancer cells, consistent with a specific antibody-mediated process. The ability of each patient’s serum to induce CDC against cultured cancer cells correlated with that patient’s survival.

Larger trials in human patients will be required to confirm the pilot study results presented here and build on the current understanding of oncolytic virotherapy and the role of CDC. In addition, further studies will need to investigate the role of other immune mechanisms, such as cell-mediated immunity, in the effects of oncolytic virus vaccines. In the meantime, the current study highlights the role of Pexa-Vec in the induction of antitumor CDC and shows its effects on survival, even in patients with late-stage cancer who have few other options.

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