Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma.
Twenty-five patients with stage IV melanoma were immunized with the mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 (2 mg per injection), which bears the internal image of the determinant defined by anti-HMW-MAA mAb 763.74. Two patients were inevaluable, since they did not complete 4 weeks of therapy. Only 14 patients developed antibodies that were shown by serological and immunochemical assays to recognize the same or spatially close determinant as the anti-HMW-MAA mAb 763.74 and to express the idiotope defined by mAb MK2-23 in their antigen-combining sites. Side effects that are likely to be caused by bacillus Calmette-Guérin present in the immunogen consisted of erythema, induration, and ulceration at the sites of the injections. Occasionally, patients complained of flu-like symptoms, arthralgias, and myalgias. Three of the patients who developed anti-HMW-MAA antibodies achieved a partial response. It consisted of a decrease in the size of metastatic lesions and lasted 52 weeks in 1 patient and 93 weeks in the other 2 patients. Survival of the 14 patients who developed anti-HMW-MAA antibodies was significantly (P = 0.0003) longer than that of the 9 patients without detectable humoral anti-HMW-MAA immunity development. In the multivariate analysis, such an association between development of anti-HMW-MAA antibodies and survival prolongation was still significant (P = 0.001) after adjustment for difference in performance status, the only confounding factor found to be significantly related to survival. Lastly, a significant (P = 0.03 by likelihood ratio test) interaction between anti-HMW-MAA antibodies and patients' performance status was found, since the prolongation of survival associated with anti-HMW-MAA antibodies was more marked in patients with a performance status of less than or equal to 70% than in those with a higher one. These results suggest that anti-idiotypic mAb MK2-23 may represent a useful immunogen to implement active specific immunotherapy in patients with melanoma.
Mittelman
A
A
Department of Medicine, New York Medical College, Valhalla 10595.
Chen
Z J
ZJ
Yang
H
H
Wong
G Y
GY
Ferrone
S
S
D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D016019:Survival Analysis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins