MURINE ANTI-ID ANTIBODIES FOR IMMUNOTHERAPY OF MELANOMA

该计划的长期目标是开发和销售鼠标 抗独特型（抗id）单克隆抗体（MoAb）， 人高分子量黑色素瘤相关抗原内部显像 （HMW-MAA）用于黑素瘤患者的主动特异性免疫治疗。 这一建议源于对BALB/c小鼠的研究， 与KLH结合并与佐剂一起给药， 增强小鼠抗id MoAb MK 2 -23诱导体液免疫应答的能力， 和对HMW-MAA的细胞免疫。 具体目标是 建议是确定与KLH和/或KLH缀合的效果， 与BCG一起施用小鼠抗id MoAb MK2-23（其具有 HMW-MAA的内部图像）对诱导体液抗HMW-MAA的影响 黑色素瘤患者的免疫力，并与黑色素瘤的发展 抗HMW-MAA免疫与疾病的临床过程。 数据 迄今为止在小鼠研究和有限的临床试验中获得的结果表明， 用带有内部免疫缺陷的抗id单克隆抗体免疫个体， HMW-MAA成像可诱导针对该抗原特异性免疫应答。 此外，临床试验表明， 抗HMW-MAA免疫和延长患者生存期。 这些 研究旨在优化免疫方案， 抗id单克隆抗体，并提供进一步的证据，这是可行的， 黑色素瘤患者的主动特异性免疫治疗方法。

The long range goal of this program is to develop and market mouse antiidiotypic (anti-id) monoclonal antibodies (MoAb) which bear the internal image of human high molecular weight-melanoma associated antigen (HMW-MAA) for active specific immunotherapy in patients with melanoma. This proposal stems from investigations in BALB/c mice which have shown that conjugation to KLH and administration with an adjuvant markedly enhances the ability of the mouse anti-id MoAb MK2-23 to induce humoral and cellular immunity towards the HMW-MAA. The specific goal of this proposal is to determine the effect of conjugation with KLH and/or administration with BCG of mouse anti-id MoAb MK2-23 (which bears the internal image of HMW-MAA) on the induction of humoral anti HMW-MAA immunity in patients with melanoma and to correlate the development of anti HMW-MAA immunity with the clinical course of the disease. The data obtained to date in mouse studies and limited clinical trials indicate that immunization of individuals with anti-id MoAb bearing the internal image of HMW-MAA can induce specific immune responses to this antigen. Moreover, the clinical trials have demonstrated an association between anti HMW-MAA immunity and prolonged patient survival. These investigations are designed to optimize the immunization protocols with anti-id MoAb and provide further evidence for the feasibility of this approach in the active specific immunotherapy of patients with melanoma.