Sano H, Kosugi A, Sano S, Fujiwara H, Hamaoka T
Department of Oncogenesis, Osaka University Medical School, Fukushima-ku, Japan.
Cancer Immunol Immunother. 1987;25(3):180-4. doi: 10.1007/BF00199145.
Preinduction of potent haptenic muramyl dipeptide (MDP)-reactive helper T cell activity and subsequent immunization with MDP hapten-coupled syngeneic tumor cells resulted in enhanced induction of tumor-specific immunity through T-T cell collaboration between anti-MDP hapten helper T cells and tumor-specific effector T cells. The present study establishes two types of tumor-specific immunotherapy protocols utilizing helper T cells against MDP hapten cross-reactive with Bacillus Calmette Guérin (BCG). In the first model, naive normal C3H/He mice or mice in which MDP hapten-reactive helper T cells had been generated by BCG-sensitization were inoculated i.d. with syngeneic X5563 tumor cells. When both groups of mice were allowed to generate MDP hapten-modified tumor cells in the tumor mass in situ by intratumoral injection of MDP hapten, an appreciable number of growing tumors in the BCG-presensitized but not in the unsensitized group were observed to regress. In the second model, a growing X5563 tumor mass was removed by the surgical resection 9 days after the tumor implantation. Approximately 90% of C3H/He mice receiving such treatment died from tumor metastasis by about 30 days after the tumor resection. However, immunization of mice with MDP hapten-coupled X5563 tumor cells subsequent to the tumor resection resulted in an increased survival rate. Such protection from the tumor metastasis was appreciably stronger when compared to the protection obtained by immunization with MDP hapten-uncoupled tumor cells. The mice surviving in both models were also demonstrated to retain X5563 tumor-specific immunity. These results indicate that the presentation of MDP hapten-modified tumor cells to BCG-sensitized recipients results in potent tumor-specific immunity which contributes to the regression of the primary tumor or inhibition of metastatic tumor growth.
预先诱导产生强效的对半抗原化胞壁酰二肽（MDP）有反应的辅助性T细胞活性，随后用MDP半抗原偶联的同基因肿瘤细胞进行免疫，通过抗MDP半抗原辅助性T细胞与肿瘤特异性效应T细胞之间的T - T细胞协作，增强了肿瘤特异性免疫的诱导。本研究建立了两种利用针对与卡介苗（BCG）交叉反应的MDP半抗原的辅助性T细胞的肿瘤特异性免疫治疗方案。在第一个模型中，将未致敏的正常C3H/He小鼠或已通过BCG致敏产生MDP半抗原反应性辅助性T细胞的小鼠经皮内接种同基因X5563肿瘤细胞。当通过瘤内注射MDP半抗原使两组小鼠在肿瘤原位肿瘤块中产生MDP半抗原修饰的肿瘤细胞时，观察到在BCG预致敏组中有相当数量正在生长的肿瘤消退，而未致敏组中则没有。在第二个模型中，肿瘤植入后9天通过手术切除生长的X5563肿瘤块。接受这种治疗的C3H/He小鼠中约90%在肿瘤切除后约30天死于肿瘤转移。然而，在肿瘤切除后用MDP半抗原偶联的X5563肿瘤细胞对小鼠进行免疫导致存活率提高。与用未偶联MDP半抗原的肿瘤细胞免疫所获得的保护相比，这种对肿瘤转移的保护明显更强。在两个模型中存活的小鼠也被证明保留了X5563肿瘤特异性免疫。这些结果表明，将MDP半抗原修饰的肿瘤细胞呈递给BCG致敏的受体可产生强效的肿瘤特异性免疫，这有助于原发性肿瘤的消退或转移性肿瘤生长的抑制。
