Kinetics of the immune response and regression of metastatic lesions following development of humoral anti-high molecular weight-melanoma associated antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypic monoclonal antibody MK2-23.
Kinetics of the immune response and regression of metastatic lesions following development of humoral anti-high molecular weight-melanoma associated antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypic monoclonal antibody MK2-23.
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发表时间：
1994-01
期刊：
影响因子：
11.2
通讯作者：
A. Mittelman;Z. J. Chen;C. Liu;S. Hirai;S. Ferrone
中科院分区：
文献类型：
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作者：
A. Mittelman;Z. J. Chen;C. Liu;S. Hirai;S. Ferrone
利用小鼠抗独特型（抗id）单克隆抗体（mAb）MK2-23，其具有高分子量黑色素瘤相关抗原（HMW-MAA）的内部图像，已在晚期恶性黑色素瘤患者中实施了主动特异性免疫治疗。在先前的研究中，发现用抗id mAb MK 2 -23免疫的晚期恶性黑素瘤患者中抗HMW-MAA免疫的发展与统计学显著的生存期延长相关。由于没有关于用抗id mAb免疫的患者中免疫发展与临床应答之间关系的信息，本研究表征了3例晚期恶性黑色素瘤患者的免疫应答动力学，这些患者在用抗id mAb MK2-23免疫后发生转移性病变消退。这三名患者产生了抗小鼠IgG抗体、抗抗id抗体和抗HMW-MAA抗体。抗HMW-MAA抗体主要为IgG，表明抗id mAb MK 2 -23引发的免疫应答是T细胞依赖性的。抗HMW-MAA免疫的发展先于转移病灶大小的减小。这种时间关系表明但不能证明抗id mAb MK2-23引发的抗HMW-MAA免疫对恶性黑色素瘤患者的疾病临床进程具有有益作用。这一发现与小鼠抗id mAb MK 2 -23重复给药相关的轻微副作用一起表明，使用带有黑素瘤相关抗原内部图像的抗id mAb进行主动特异性免疫治疗代表了恶性黑素瘤的可行治疗方法。
Active specific immunotherapy has been implemented in patients with advanced malignant melanoma, utilizing the mouse antiidiotypic (anti-id) monoclonal antibody (mAb) MK2-23 which bears the internal image of high molecular weight-melanoma associated antigen (HMW-MAA). In a previous study, development of anti-HMW-MAA immunity in patients with advanced malignant melanoma immunized with anti-id mAb MK2-23 was found to be associated with a statistically significant survival prolongation. Since no information is available about the relationship between development of immunity and clinical response in patients immunized with anti-id mAb, the present study has characterized the kinetics of the immune response in three patients with advanced malignant melanoma who experienced regression of metastatic lesions following immunization with the anti-id mAb MK2-23. The three patients developed anti-mouse IgG antibodies, anti-anti-id antibodies and anti-HMW-MAA antibodies. The anti-HMW-MAA antibodies are mainly IgG, suggesting that the immune response elicited by anti-id mAb MK2-23 is T-cell dependent. The development of anti-HMW-MAA immunity preceded the reduction in the size of metastatic lesions. This temporal relationship suggests but does not prove that the anti-HMW-MAA immunity elicited by anti-id mAb MK2-23 has a beneficial effect on the clinical course of the disease in patients with malignant melanoma. This finding in conjunction with minor side effects associated with repeated administrations of mouse anti-id mAb MK2-23 suggest that active specific immunotherapy with anti-id mAb which bear the internal image of melanoma-associated antigen represents a viable therapeutic approach to malignant melanoma.