Fujiwara H, Takai Y, Fukuzawa M, Yoshioka T, Izumi Y, Mizushima Y, Qian J, Ogata M, Kosugi A, Nakajima H
Gan To Kagaku Ryoho. 1985 Mar;12(3 Pt 2):734-40.
The present study establishes a tumor-specific immunotherapy model based on the principle of T-T cell interaction mechanism responsible for augmenting the induction of anti-tumor-specific effector T cells. In this model, high incidence of tumor regression was observed in hosts bearing transplantable or autochthonous tumors when these hosts, in which hapten-reactive helper T cells had been generated, received an injection of haptenic solution into the growing tumor mass. This indicated a role of hapten-reactive helper T cells in regressing the tumor. In consideration clinical application of this tumor-specific immunotherapy model, we have also tried to investigate the use of more appropriate haptenic compounds and have succeeded in synthesizing a noble haptenic compound cross-reactive with BCG, a haptenic muramyl dipeptide (MDP) derivative. The results demonstrated that prepriming of BCG and subsequent immunization with syngeneic tumor cells (mitomycin C-treated) modified with the haptenic MDP derivative resulted in the enhanced induction of tumor-specific immunity. Further investigation is in progress to establish a new tumor-specific immunotherapy model by utilizing this haptenic MDP derivative.
本研究基于负责增强抗肿瘤特异性效应T细胞诱导的T-T细胞相互作用机制原理,建立了一种肿瘤特异性免疫治疗模型。在该模型中,当已产生半抗原反应性辅助性T细胞的宿主,向生长中的肿瘤块注射半抗原溶液时,在携带可移植或自体肿瘤的宿主中观察到高比例的肿瘤消退。这表明半抗原反应性辅助性T细胞在肿瘤消退中发挥了作用。考虑到该肿瘤特异性免疫治疗模型的临床应用,我们还尝试研究使用更合适的半抗原化合物,并成功合成了一种与卡介苗交叉反应的新型半抗原化合物,一种半抗原化的胞壁酰二肽(MDP)衍生物。结果表明,卡介苗预致敏以及随后用半抗原化MDP衍生物修饰的同基因肿瘤细胞(丝裂霉素C处理)进行免疫,可增强肿瘤特异性免疫的诱导。利用这种半抗原化MDP衍生物建立新的肿瘤特异性免疫治疗模型的进一步研究正在进行中。