Citations 1
Oncolytic Alphaherpesvirus and Myeloid-Tropic Cytomegalovirus Cooperatively Enhance Systemic Antitumor Responses
Jiang, Haifei , Nace, Rebecca A., Ariail, Emily , Ma, Yejun, McGlinch, Erin B. , Ferguson, Coryn, Carrasco, Talia Fernandez, Zhang, Lianwen , Peng, Kah Whye, Packiriswamy, Nandakumar
No container title available | April 17, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Oncolytic virotherapy aims to activate host antitumor immunity, but the effectiveness of current intratumoral herpes-simplex virus (HSV) based monotherapy is limited. Here, to boost the potency of cancer cell targeting α-herpesviruses derived from HSV or Varicella-Zoster Virus (VZV), we coinjected them with myeloid cell-tropic β-herpesviruses derived from cytomegalovirus (CMV) which can powerfully modulate immune responses. Co-administered CMV was shown to promote intratumoral replication of HSV, increase local release of pro-inflammatory cytokines, inhibit adaptive antiviral immune responses, enhance systemic antitumor responses, and lead to superior control of both injected and contralateral tumors. CMV-encoded myeloid-tropic genes, NK evasins (i.e. the vMHC-I homolog), and the m02-m16 region (involved in downregulating classical MHC-I) were implicated in enhancing antitumor activities. CMV is a promising adjuvant to reshape and enhance the antitumor immune responses following α-herpesvirus therapy.