Direct vaccination with tumor cells killed with ICP4-deficient HSVd120 elicits effective antitumor immunity.
We tested whether tumor cells were killed by replication-incompetent recombinant herpes simplex virus (HSV) d120 lacking immediate early gene ICP4 and whether HSVd120-killed tumor cells could be used directly for tumor vaccination. Vaccine efficacy was tested in TC-1, a murine adenocarcinoma transformed with HPV16 E6 and E7, and ID8-Vegf, a murine epithelial ovarian cancer model. HSVd120 killed tumor cells by apoptosis. Tumor cells infected by HSVd120 were engulfed more avidly by immature DCs and induced DC maturation more efficiently than tumor cells killed by ultraviolet B (UVB) radiation. HSVd120 infection induced stronger upregulation of GRP94 than UVB in cells undergoing apoptosis. Immunization of mice with HSVd120-killed cells elicited stronger antitumor T cell response, including tumor reactive interferon-gamma secreting and cytotoxic T cells, and resulted in significantly stronger delay in tumor growth than immunization with UVB-killed tumor cells. Thus, the use of replication-incompetent HSV strains lacking ICP4 offers possible advantages in the preparation of whole tumor cell antigen for direct tumor vaccination.
Benencia
Fabian
F
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Courrèges
Maria C
MC
Conejo-García
José R
JR
Mohammed-Hadley
Alisha
A
Coukos
George
G
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D017874:Immediate-Early Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D018139:Simplexvirus / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation; D014611:Vaccination / Q000379:methods; D014779:Virus Replication / Q000235:genetics
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin; C048925:herpes simplex virus, type 1 protein ICP4