溶瘤病毒
溶癌病毒
免疫疗法
免疫系统
抗原
免疫学
医学
单纯疱疹病毒
免疫
T细胞
病毒学
病毒
癌症研究
作者
Stacie K. Totsch,Andrew S. Ishizuka,Kyung-Don Kang,Sam E. Gary,Abbey Rocco,Aaron E. Fan,Li Zhou,Pablo A. Valdés,Seung Ho Lee,Jason Li,Luca Peruzzotti‐Jametti,Sarah 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]
日期:2024-05-06
标识
DOI:10.1158/1535-7163.mct-23-0873
摘要
Abstract Purpose: 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 (oHSVs) 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. Experimental Design: To this end, we investigated the preclinical efficacy and potential synergy of combining oHSV with a self-assembling nanoparticle vaccine co-delivering peptide antigens and Toll-like receptor-7 and -8 agonists (TLR-7/8a) (referred to as SNAPvax™), that 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. Results: 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 tumour volume and increases in virus replication and tumor antigen specific CD8+ T cells. Conclusions: 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI