权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

AntiーCD3 Monoclonal Antibody and IL-2 Induced Cytotoxicity of T Lymphocytes from Oral Cancer Patients.

抗 CD3 单克隆抗体和 IL-2 诱导口腔癌患者 T 淋巴细胞的细胞毒性。

基本信息

批准号：
01571088
负责人：
TAKAHASHI Yuzo
金额：
$ 1.34万
依托单位：
Faculty of Dentistry, Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

A Grest number of cells, which have high level of cytotoxic activity, are demanded for successful adoptive immunotherapy with Lymphokine-Activated Killer (LAK) cells. We attempted to make culture CD3-LAK cells using anti-CD3 monoclonal antibody and interleukin-2, and investigated how the proliferative response and cytotoxic activity of LAK cells (CD3・LAK) are affected by BRM (cytokines, OK432, etc.). In clinically, therapeutic effects of the combination of radiation therapy, chemotherapy and adoptive immunotherapy are expected, therefor, we investigated the effect of these therapy on CD3-LAK cells.1. Induction of CD3・LAK cells : High proliferative response and cytotoxic activity were induced from peripheral blood lymphocytes (PBL) by using anti-CD3 monoclonal antibody and IL-2.2. The effect of cytokines (rIFNgamma, rTNF alpha, rG-CSF, rIL-1 alpha, rIL-1beta) on CD3・LAKcells : Proliferative response of CD3・LAK cells increased by rTNFalpha at low concentration of rIL-2. Cytotoxic activity of these cells were not affected by any cytokines. At the first stage of CD・LAK induction, OK432 significantly enhanced cytotoxic activity of these cells.3. The effect of antineoplastic agent (CDDP, 5-FU, MTX, PEP, BLM, ADR) and irradiation (1.25, 2.5, 5.0, 10.0, 20.0Gy) on CD3・LAK cells : Proliferative response of CD3-LAK cells were suppressed by both antineoplastic agent and irradiation.Cytotoxic activiy of these cells were neither affected by antineoplastic agent nor irradiation.These results indicate that LAK induction using together anti-CD3 monoclonal antibody with rIL-2 is available for adoptive immunotherapy on oral cancer patients, and that therapeutic effects of adoptive immunotherapy in combination with chemotherapy and radiation therapy are expected.

成功的过继免疫治疗需要大量具有高水平细胞毒活性的LAK细胞。本实验尝试用抗CD 3单克隆抗体和白细胞介素2（IL-2）培养CD 3-LAK细胞，观察BRM（细胞因子、OK 432等）对LAK细胞增殖反应和细胞毒活性的影响。在临床上，放疗、化疗和过继免疫治疗的联合应用有望取得较好的疗效，为此，我们研究了这些治疗方法对CD 3-LAK细胞的影响. CD 3·LAK细胞的诱导：用抗CD 3单克隆抗体和IL-2.2诱导外周血淋巴细胞（PBL）产生高增殖反应和细胞毒活性。细胞因子（rIFN γ、rTNF α、rG-CSF、rIL-1 α、rIL-1 β）对CD 3·LAK细胞的作用：低浓度rIL-2时rTNF α可增强CD 3·LAK细胞的增殖反应。这些细胞的细胞毒性活性不受任何细胞因子的影响。在CD·LAK诱导的第一阶段，OK 432显著增强了这些细胞的细胞毒活性.杀菌剂的作用（CDDP、5-FU、MTX、PEP、BLM、ADR）和照射（1.25、2.5、5.0、10.0、20.0Gy）对CD_3·LAK细胞的杀伤作用：CD 3-T细胞的免疫应答LAK细胞的杀伤活性受照射和化疗剂的双重抑制，但不受化疗剂和放疗的影响，提示用化疗剂诱导LAK细胞是可行的。抗CD 3单克隆抗体与rIL-2联合应用可用于口腔癌患者的过继免疫治疗，并可期待过继免疫治疗联合化疗和放疗的治疗效果。