HUMAN HIGH-MOLECULAR WEIGHT-MELANOMA ASSOCIATED ANTIGEN MIMICRY BY MOUSE ANTIIDIOTYPIC MONOCLONAL-ANTIBODY MK2-23 - MODULATION OF THE IMMUNOGENICITY IN PATIENTS WITH MALIGNANT-MELANOMA

The mouse anti-idiotypic (anti-id) mAb MK2-23 bears the mirror image o f the antigenic determinant defined by antihuman high molecular weight -melanoma associated antigen (HMW-MAA) mAb 763.74. The purpose of this study was to evaluate the effect of conjugation to a carrier and admi nistration with an adjuvant and cyclophosphamide (CTX) on the immunoge nicity of anti-id mAb MK2-23 in patients with malignant melanoma and t o analyze the relationship between development of humoral immunity and survival time of patients, Fifty-eight patients were sequentially ent ered into four immunization protocols which included administration of mAb MK2-23, mAb MK2-23 conjugated to keyhole limpet hemocyanin (KCH) and mixed with Bacillus Calmette-Guerin (BCG), mAb MK2-23 and CTX, and mAb MK2-23 conjugated to KLH and mixed with BCG and CTX, Six patients could not be evaluated since they withdrew from the clinical trial af ter the first immunization, Sera were tested for the development of an ti-anti-id antibodies, including those reacting with HMW-MAA, Testing of sera for development of antimouse Ig antibodies was used to monitor the immune competence of patients. Conjugation to KLH and administrat ion with BCG markedly enhanced the ability of mAb MK2-23 to induce ant i-anti-id antibodies, including those reacting with HMW-MAA. In contra st, pretreatment with CTX had no detectable effect on the ability of m Ab MK2-23 to elicit a humoral anti-anti-id response, Kaplan-Meier surv ival analysis showed that the performance status of patients, anti-ant i-id antibody level, and development of anti-HMW-MAA antibodies had an effect on survival time, This effect was found when the survival time was calculated both from the day of the first immunization and from 4 weeks after the first immunization to the end of the study, A multiva riate analysis by Cox regression showed that the development of anti-H MW-MAA antibodies was the most important variable for predicting survi val, and that performance status was the only variable that significan tly added to the prediction of survival, These data have to be interpr eted with caution because of the retrospective nature of the analysis, Nevertheless, the present study suggests that mAb MK2-23 represents a useful immunogen to implement active, specific immunotherapy in patie nts with malignant melanoma.