IMMUNOTHERAPY OF MALIGNANT BRAIN TUMORS USING OK-432-ACTIVATED MONONUCLEAR CELLS COMBINED WITH HUMAN MONOCLONAL ANTIBODY AGAINST CANCER

局部应用OK-432激活的杀伤细胞（OK-AK）对大多数恶性脑肿瘤患者有效。在这种疗法中，自然杀伤（NK）细胞是主要的效应细胞。最近，主要组织相容性（MHC）I类表达和靶细胞对NK细胞介导的裂解的易感性之间的负相关性已被报道。我们研究了人胶质母细胞瘤细胞在表达和不表达MHC Ⅰ类抗原的条件下对NK细胞的敏感性，结果表明，OK-AK细胞只裂解人胶质母细胞瘤细胞，而胶质母细胞瘤细胞表面表达MHC Ⅰ类抗原可明显降低其对NK细胞裂解的敏感性。人抗肿瘤单克隆抗体（CLN-IgG）与恶性胶质瘤的结合多于与低级别胶质瘤的结合。CLN-IgG可增强表达MHC Ⅰ类抗原的胶质母细胞瘤细胞对NK细胞杀伤的敏感性，提示CLN-IgG可增强OK-AK细胞对恶性胶质瘤的杀伤作用。

Local administration of OK-432-activated killer (OK-AK) cells has been effective in most patients with malignant brain tumor. In this therapy natural killer(NK) cells are the main effector cells. Recently the inverse correlation between major histocompatibility (MHC) class I expression and susceptibility of target cells to NK cell-mediated lysis has been reported. We exmained the sensitivity of human glioblastoma cells under MHC class I-expressing and the non-expressing conditions.Our results showed that OK-AK cells exclusively lysed the human gliobalstoma cells and that the susceptibility of glioblastoma cells to NK lysis was markedly reduced by the expression of MHC class I antigens on their cell surface. Human monoclonal antibody against cancer (CLN-IgG) was bound to malignant gliomans more than to low-grade gliomas. The susceptibility of glioblastoma cells with the expression of MHC class I antigens to NK lysis was improved by the administration of CLN-IgG.The present results indicate that CLN-IgG may enhance the cytocidal effect of OK-AK cells against malignant gliomas.