Induction of cellular immune responses by a murine monoclonal anti-idiotypic antibody recognizing the 791tgp72 antigen expressed on colorectal, gastric and ovarian human tumours
✍ Scribed by Lindy G. Durrant; Mark Doran; Eric B. Austin; R. Adrian Robins
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 525 KB
- Volume
- 61
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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) I05AD7 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 79 IT/36, induced DTH responses to 79 I Tgp72-expressing tumour cells but not to antigen-negative cells. DTH responses with no detectable antibody responses were induced with 5 Fg of anti-id NCRC6O without adjuvant. Addition of either complete Freund's adjuvant or Quil A did not enhance DTH responses. However, when the anti-id NCRCIO was linked to KLH and injected in the presence of Freund's adjuvant antianti-id antibodies and anti-79 ITgp72 antibodies were induced. NCRC6O anti-id was also capable in vitro of priming human T cells from cancer patients to proliferate in response to secondary stimulation with 79 I Tgp72-expressing tumour cells, suggesting that it may have therapeutic potential in cancer patients.