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

OK-432激活的单核细胞联合抗癌人单克隆抗体对恶性脑肿瘤的免疫治疗

• 批准号: 04670866
• 负责人: ABE Masamitsu
• 金额: $ 1.28万
• 依托单位: SAGA MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670866/
• 关键词: Glioma; MHC; Immunotherapy; Monoclonal antibody; Cytokine; glioma; immunotherapy; monoclonal antibody; cytokine; CLN-IgG; OK-432 activated killer cell; MHC class I; ^<51>Cr release assay; Flowcytometry; Immunohistochemical stain

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.

局部应用OK-432激活的杀伤细胞(OK-AK)对大多数恶性脑瘤患者有效。在该疗法中，自然杀伤(NK)细胞是主要的效应细胞。最近有报道称，主要组织相容性(MHC)I类分子的表达与靶细胞对NK细胞介导的杀伤的易感性呈负相关。结果表明，OK-AK细胞对人胶质母细胞瘤细胞具有特异性杀伤作用，其细胞表面MHC-I类抗原的表达显著降低了胶质母细胞瘤细胞对NK杀伤的敏感性。人源性抗癌单抗(CLN-Ig G)与恶性胶质瘤结合的能力强于与低级别胶质瘤的结合。CLN-Ig G可提高表达MHC-I类抗原的胶质母细胞瘤细胞对NK杀伤的敏感性。提示CLN-Ig G可增强OK-AK细胞对恶性胶质瘤的杀伤作用。

项目成果

阿部雅光: "先端巨大症とクッシング病に対する定位的陽子線治療" ホルモンと臨床. 40. 110-113 (1992)

Masamitsu Abe：“肢端肥大症和库欣病的立体定向质子疗法”《激素与临床科学》40. 110-113 (1992)。

田渕和雄: "脳腫瘍の遺伝子診断" 脳と神経. 44. 871-879 (1992)

Kazuo Tabuchi：“脑肿瘤的基因诊断”《大脑与神经》44. 871-879 (1992)。

田渕和雄: "脳腫瘍の分子生物学的特性" 脳神経外科. 21. 677-696 (1993)

Kazuo Tabuchi：“脑肿瘤的分子生物学特征”《神经外科》21. 677-696 (1993)。

Tabuchi K.: "Altered structure and expression of the p53 gene in human neuroepithelial tumors." Neurol.Med.Chir.32. 725-732 (1992)

Tabuchi K.：“人类神经上皮肿瘤中 p53 基因的结构和表达发生了改变。”

Momozaki N., Oh-uchida M., Tabuchi K., Ikezaki K.and Hori K.: "Suppression of anchorage-independent growth of human glioblastoma by major histocompatibility complex class I gene-transfection." J.Neurosurg.76. 845-849 (1992)

Momozaki N.、Oh-uchida M.、Tabuchi K.、Ikezaki K. 和 Hori K.：“通过主要组织相容性复合体 I 类基因转染抑制人类胶质母细胞瘤的锚定非依赖性生长。”