Idiotypic immunization induces immunity to mutated p53 and tumor rejection.
The p53 molecule might serve as a common tumor-associated antigen, as the tumor suppressor gene p53 is mutated and the p53 protein is often over-expressed in tumor cells. We report that effective immunity to p53 can be induced through an idiotypic network by immunization of mice with a monoclonal antibody (PAb-240) specific for mutated p53, or with a peptide derived from the complementarity determining region (CDR) 3 of the variable domain of the light chain (VL) of this antibody. The immunized mice produced IgG antibodies to p53 and mounted a cytotoxic reaction to a tumor line bearing mutated p53. The idiotypically immunized mice were resistant to challenge with the tumor cells. Thus antibodies to p53 might serve as immunogens for activating resistance to some tumors. At the basic level, these findings indicate that a network of p53 immunity may be organized naturally within the immune system.
Ruiz
P J
PJ
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, California 94305-5429, USA.
Wolkowicz
R
R
Waisman
A
A
Hirschberg
D L
DL
Carmi
P
P
Erez
N
N
Garren
H
H
Herkel
J
J
Karpuj
M
M
Steinman
L
L
Rotter
V
V
Cohen
I R
IR
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D000939:Epitopes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D007109:Immunity / Q000187:drug effects; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D009368:Neoplasm Transplantation / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000503:physiopathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D009842:Oligopeptides; D016159:Tumor Suppressor Protein p53