Anti-idiotype responses abrogate anti-CD4-induced tolerance to a tumor-specific antigen and promote systemic tumor immunity.
OBJECTIVE
Immunologic-based cancer treatment modalities represent an active area of investigation. Included in these strategies are passive administration of monoclonal antibodies which recognize tumor-associated antigens and active vaccination with identified tumor antigens. However, several problems associated with these types of treatment strategies have been identified.


METHODS
In this report, we address certain issues by employing a murine model for experimental pulmonary metastasis and a tumor antigen vaccination strategy that induces complete tumor immunity in this system. Utilizing this model, we attempt to address issues related to unresponsiveness to tumor antigen immunization induced by passive administration of a rat monoclonal anti-CD4 and the induction of anti-idiotype responses to a passively administered monoclonal antibody and the effects on the induction of tumor immunity.


RESULTS
The results presented indicate that passive administration of rat monoclonal anti-CD4 exhibits immunosuppressive effects that inhibit the production of antibodies to the tumor antigen immunization and abolishes tumor immunity. Repeated administration of the rat monoclonal anti-CD4 results in an anti-idiotype response that can abrogate unresponsiveness to tumor antigen immunization and promote systemic tumor immunity.


CONCLUSIONS
The data examine a number of potential problems associated with immunologic-based treatments for cancer. These problems include the potential for tolerance to the tumor antigen and establishing an immunocompromised state where immunization with a tumor antigen failed to generate tumor immunity. Approaches to eliminate tolerant T cells by targeting anti-CD4 via anti-idiotype responses that could be generated in vivo without CD4+ T cells allowed for recovery of nontolerant T cells, and an antibody response to the tumor antigen that results in tumor immunity.
Kennedy
Ronald C
RC
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. ronald.kennedy@ttuhsc.edu
Shearer
Michael H
MH
Lowe
Devin B
DB
Jumper
Cynthia A
CA
Chiriva-Internati
Maurizio
M
Bright
Robert K
RK
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000737:chemistry*; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000737:chemistry*; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000737:chemistry; D007130:Immunoglobulin Idiotypes; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes