Dendritic cells transduced with wild-type p53 gene elicit potent anti-tumour immune responses.
In this study we have tested the concept of using wild-type p53 gene for immunotherapy of cancer. Dendritic cells (DC) were transduced with a human wild-type p53 containing recombinant adenovirus (Ad-p53). About a half of DC transduced with this virus expressed p53 protein by FACS analysis 48 h after infection. Mice immunized twice with Ad-p53 DC developed substantial cytotoxic T lymphocyte (CTL) responses against tumour cells expressing wild-type and different mutant human and murine p53 genes. Very low CTL responses were observed against target cells infected with control adenovirus (Ad-c). Immunization with Ad-p53 provided complete tumour protection in 85% of mice challenged with tumour cells expressing human mutant p53 and in 72.7% of mice challenged with tumour cells with murine mutant p53. Treatment with Ad-p53-transduced DC significantly slowed the growth of established tumours. Thus, DC transduced with wild-type p53 may be a promising new tool for the immunotherapy of cancer.
Ishida
T
T
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Chada
S
S
Stipanov
M
M
Nadaf
S
S
Ciernik
F I
FI
Gabrilovich
D I
DI
Carbone
D P
DP
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016158:Genes, p53 / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D014162:Transfection / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019496:Cancer Vaccines