Combination Immunotherapy with Vaccine and Oncolytic HSV Virotherapy Is Time Dependent

溶瘤病毒 溶癌病毒 免疫疗法 免疫系统 免疫学 医学 HSL和HSV色彩空间 病毒学 病毒
作者
Stacie K. Totsch,Andrew S. Ishizuka,Kyung‐Don Kang,Sam E. Gary,Abbey Rocco,Aaron E. Fan,Li Zhou,Pablo A. Valdés,SeungHo Lee,Jason Li,Luca Peruzzotti‐Jametti,Sarah E. Blitz,Christopher M. Garliss,James M. Johnston,James M. Markert,Geoffrey M. Lynn,Joshua D. Bernstock,Gregory K. Friedman
出处
期刊:Molecular Cancer Therapeutics [American Association for Cancer Research]
卷期号:23 (9): 1273-1281
标识
DOI:10.1158/1535-7163.mct-23-0873
摘要

Abstract Oncolytic virotherapy or immunovirotherapy is a strategy that utilizes viruses to selectively infect and kill tumor cells while also stimulating an immune response against the tumor. Early clinical trials in both pediatric and adult patients using oncolytic herpes simplex viruses (oHSV) have demonstrated safety and promising efficacy; however, combinatorial strategies designed to enhance oncolysis while also promoting durable T-cell responses for sustaining disease remission are likely required. We hypothesized that combining the direct tumor cell killing and innate immune stimulation by oHSV with a vaccine that promotes T cell–mediated immunity may lead to more durable tumor regression. To this end, we investigated the preclinical efficacy and potential synergy of combining oHSV with a self-assembling nanoparticle vaccine codelivering peptide antigens and Toll-like receptor 7 and 8 agonists (referred to as SNAPvax),which induces robust tumor-specific T-cell immunity. We then assessed how timing of the treatments (i.e., vaccine before or after oHSV) impacts T-cell responses, viral replication, and preclinical efficacy. The sequence of treatments was critical, as survival was significantly enhanced when the SNAPvax vaccine was given prior to oHSV. Increased clinical efficacy was associated with reduced tumor volume and increases in virus replication and tumor antigen–specific CD8+ T cells. These findings substantiate the criticality of combination immunotherapy timing and provide preclinical support for combining SNAPvax with oHSV as a promising treatment approach for both pediatric and adult tumors.
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