Induction of cellular immune responses by a murine monoclonal anti-idiotypic antibody recognizing the 791Tgp72 antigen expressed on colorectal, gastric and ovarian human tumours

Int J Cancer. 1995 Mar 29;61(1):62-6. doi: 10.1002/ijc.2910610111.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / pharmacology*
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, Neoplasm / immunology*
  • Colorectal Neoplasms / immunology*
  • Dose-Response Relationship, Drug
  • Drug Hypersensitivity / etiology
  • Drug Hypersensitivity / immunology
  • Female
  • Glycoproteins / immunology*
  • Humans
  • Hypersensitivity, Delayed / chemically induced
  • Hypersensitivity, Delayed / immunology
  • Immunity, Cellular / drug effects
  • Immunization
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Ovarian Neoplasms / immunology*
  • Stomach Neoplasms / immunology*
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Glycoproteins
  • tumor-associated antigen 72