Human high molecular weight-melanoma associated antigen mimicry by mouse anti-idiotypic monoclonal antibodies MK2-23. Experimental studies and clinical trials in patients with malignant melanoma

Abstract

Following a description of the characteristics of the human high molecular weight-melanoma associated antigen (HMW-MAA), the rationale to use anti-idiotypic (anti-id) monoclonal antibodies (mAb) as immunogens to implement active specific immunotherapy in patients with malignant diseases is discussed. Among the anti-id mAb developed in this laboratory the mAb MK2-23, which had been elicited with the syngeneic anti-HMW-MAA mAb 763.74, has been shown with serological and immunochemical assays to bear the mirror image of the determinant recognized by mAb 763.74 on HMW-MAA. The anti-id mAb elicited humoral anti-HMW-MAA immunity in about 60% of patients with malignant melanoma. The immunogenicity of mAb MK2-23 is markedly enhanced by conjugation to a carrier and administration with an adjuvant, but is not affected by the administration of low doses of cyclophosphamide. Development of anti-HMW-MAA immunity in patients with malignant melanoma is associated with survival prolongation. These results in conjunction with the lack of major side effects in spite of repeated administrations of mAb MK2-23 suggest that active specific immunotherapy with mAb MK2-23 represents a useful therapeutic approach to malignant melanoma.