Chen J J, Saeki Y, Shi L F, Köhler H
Department of Microbiology, State University of New York, Buffalo 14214.
J Immunol. 1989 Aug 1;143(3):1053-7.
Anti-Id antibodies that have biologic activity as stimulators of specific immunity have been used in experimental vaccines and tumor protection models. However, very little is known about the therapeutic potential of anti-Id antibodies in animals and men. In this study we explored the combination of anti-Id and chemotherapy in a murine tumor system for which we had previously generated protective anti-Id mAb. First, we investigated various protocols by using a protective anti-Id in active immunization. Mice preimmunized before tumor transfer and challenged again after tumor survived significantly longer. Next, we explored the use of soluble anti-Id as immunostimulator in tumor-bearing mice. Although this treatment did not induce long-term survival, it significantly increased survival time. Interestingly, this anti-Id effect was dose dependent, whereby large and small doses had no effect. Finally, stimulatory anti-Id therapy and cyclophosphamide (Cy) treatment was combined. Tumor bearing mice were given a single dose of Cy followed by different doses of soluble anti-Id. The optimal effect on tumor growth and survival was achieved with 80 mg/kg Cy and 10 micrograms/mouse of anti-Id, where 80% of mice survived longer than 100 days. These results provide guidelines for developing clinical protocols for cancer patients by using combination therapy of anti-Id and chemotherapy.
具有作为特异性免疫刺激剂的生物活性的抗独特型抗体已被用于实验性疫苗和肿瘤保护模型中。然而，关于抗独特型抗体在动物和人类中的治疗潜力，人们所知甚少。在本研究中，我们在一个小鼠肿瘤系统中探索了抗独特型抗体与化疗的联合应用，此前我们已在该系统中制备出具有保护作用的抗独特型单克隆抗体。首先，我们在主动免疫中使用具有保护作用的抗独特型抗体研究了各种方案。在肿瘤移植前预先免疫且在肿瘤接种后再次受到攻击的小鼠存活时间显著延长。接下来，我们在荷瘤小鼠中探索了使用可溶性抗独特型抗体作为免疫刺激剂。尽管这种治疗并未诱导长期存活，但它显著延长了存活时间。有趣的是，这种抗独特型抗体的效应是剂量依赖性的，大剂量和小剂量均无效果。最后，将刺激性抗独特型抗体疗法与环磷酰胺（Cy）治疗相结合。给荷瘤小鼠单次注射Cy，随后给予不同剂量的可溶性抗独特型抗体。使用80mg/kg的Cy和10μg/只小鼠的抗独特型抗体对肿瘤生长和存活产生了最佳效果，其中80%的小鼠存活时间超过100天。这些结果为通过抗独特型抗体与化疗的联合疗法制定癌症患者的临床方案提供了指导。
