| 1861071 |
Chen ZJ, Yang H, Ferrone S: Human high molecular weight melanoma-associated antigen mimicry by mouse antiidiotypic monoclonal antibody MK2-23. J Immunol. 1991 Aug 1;147(3):1082-90.
Characterization of the immunogenicity in syngeneic hosts.. Previous studies have shown that the mouse antiidiotypic mAb MK2-23 elicited with the syngeneic anti-human high molecular weight melanoma-associated Ag (HMW-MAA) mAb 763.74 elicits anti-HMW-MAA antibodies in syngeneic hosts and in patients with melanoma. The present investigation has characterized the fine specificity of antibodies elicited by mAb MK2-23, tested its ability to induce delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells and analyzed the variables that influence the immunogenicity of mAb MK2-23. The anti-HMW-MAA antibodies elicited by mAb MK2-23 recognize the same population of molecules recognized by mAb 763.74, react with the same (or spatially close) determinant (s) and express the idiotopes recognized by mAb MK2-23 in their Ag-combining sites. The antiidiotypic antibodies that bind to HMW-MAA have a lower titer than those that do not. These results in conjunction with those obtained in mice using a suboptimal immunization schedule suggest that the idiotope (s) that mimic (s) the mAb 763.74-defined determinant of the HMW-MAA is less immunogenic than those that do not. mAb MK2-23 induces a delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells. Therefore, mAb MK2-23 represents the first example of mouse antiidiotypic mAb that induces a cellular and humoral immunity to a human tumor-associated Ag (TAA), because the previously described mouse antiidiotypic mAb that bear the mirror image of TAA have been shown to induce only humoral anti-TAA immunity. The immunogenicity of mAb MK2-23 is markedly enhanced by its conjugation to keyhole limpet hemocyanin and its administration with FA. Furthermore, the number of immunizations and the doses of mAb MK2-23 injected influence its immunogenicity, although to a lower extent than conjugation to a carrier and mixing with an adjuvant. The information derived from the present investigation represents a useful background to optimize the immunization schedule with mAb MK2-23 in patients with melanoma. |
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