Induction of cellular immune responses by a murine monoclonal anti-idiotypic antibody recognizing the 791Tgp72 antigen expressed on colorectal, gastric and ovarian human tumours.
There is accumulating evidence that cellular rather than antibody responses are more effective for tumour rejection. It is therefore important to screen anti-idiotypic (anti-id) antibodies for their ability to stimulate anti-tumour T-cell responses. The human anti-id monoclonal antibody (MAb) 105AD7 stimulated both delayed-type hypersensitivity (DTH) responses in animals and antigen-specific blastogenesis and IL-2 induction in advanced cancer patients. It may not be necessary to use human anti-id antibodies as murine anti-id antibodies, which elicit DTH responses against immunodominant human T-cell epitopes and may be just as useful in the clinic. We have therefore produced a murine anti-id antibody to the same MAb as was used to generate the human anti-id antibody and screened it for its ability to generate cellular anti-tumour immune responses. Low-dose immunization with the murine anti-id MAb NCRC60, which recognises the paratope of the anti-791Tgp72 MAb 791T/36, induced DTH responses to 791Tgp72-expressing tumour cells but not to antigen-negative cells. DTH responses with no detectable antibody responses were induced with 5 micrograms of anti-id NCRC60 without adjuvant. Addition of either complete Freund's adjuvant or Quil A did not enhance DTH responses. However, when the anti-id NCRC60 was linked to KLH and injected in the presence of Freund's adjuvant anti-anti-id antibodies and anti-791Tgp72 antibodies were induced. NCRC60 anti-id was also capable in vitro of priming human T cells from cancer patients to proliferate in response to secondary stimulation with 791Tgp72-expressing tumour cells, suggesting that it may have therapeutic potential in cancer patients.
Durrant
L G
LG
Department of Surgery, University of Nottingham, UK.
Doran
M
M
Austin
E B
EB
Robins
R A
RA
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; C047052:tumor-associated antigen 72