Requirement of an integrated immune response for successful neuroattenuated HSV-1 therapy in an intracranial metastatic melanoma model.
Neuroattenuated herpes simplex virus ICP34.5 mutants slow progression of preformed tumors and lead to complete regression of some tumors. Although this was previously thought to be due to viral lysis of infected tumor cells, it is now understood that there is an immune component to tumor destruction. We have previously shown that no difference in survival is seen in lymphocyte-depleted mice after viral or mock therapy of syngeneic intracranial melanomas. We have also demonstrated the presence of a wide spectrum of immune cells following viral therapy, including larger percentages of CD4+ T cells and macrophages. In this paper, the contribution of the immune system to tumor destruction has been further delineated. Viral therapy of intracranial melanoma induces a tumor-specific cytotoxic and proliferative T cell response. However, there is no increase following viral therapy in either serum tumor antibody levels or viral-neutralizing antibodies. Thus specific T cell responses appear to mediate viral-elicited prolongation in survival. These data suggest that designing new viruses capable of augmenting T cell responses may induce stronger tumor destruction upon viral therapy.
Miller
Cathie G
CG
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
Fraser
Nigel W
NW
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005260:Female; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage*
D015704:CD4 Antigens; D016827:CD8 Antigens; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D022301:Herpes Simplex Virus Vaccines; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D014613:Vaccines, Attenuated