Ferrone S, Chen Z J, Liu C C, Hirai S, Kageshita T, Mittelman A
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Pharmacol Ther. 1993 Feb-Mar;57(2-3):259-90. doi: 10.1016/0163-7258(93)90058-l.
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.
在描述了人类高分子量黑色素瘤相关抗原（HMW-MAA）的特征之后，讨论了使用抗独特型（抗-Id）单克隆抗体（mAb）作为免疫原对恶性疾病患者实施主动特异性免疫治疗的基本原理。在本实验室开发的抗-Id mAb中，用同基因抗HMW-MAA mAb 763.74诱导产生的mAb MK2-23，经血清学和免疫化学分析显示，其具有与mAb 763.74在HMW-MAA上识别的决定簇的镜像结构。抗-Id mAb在约60%的恶性黑色素瘤患者中诱导出体液抗HMW-MAA免疫。mAb MK2-23与载体偶联并与佐剂一起给药时，其免疫原性显著增强，但不受低剂量环磷酰胺给药的影响。恶性黑色素瘤患者抗HMW-MAA免疫的产生与生存期延长相关。尽管反复给予mAb MK2-23，但仍缺乏主要副作用，这些结果表明，用mAb MK2-23进行主动特异性免疫治疗是治疗恶性黑色素瘤的一种有用方法。
