Studies on Adoptive Immunotherapy Utilizing Allogeneic Spleen Cells Against Cancers

利用同种异体脾细胞对抗癌症的过继免疫疗法的研究

• 批准号: 03670949
• 负责人: KUBOTA Eiro
• 金额: $ 1.34万
• 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670949/
• 关键词: Allogeneic spleen cells; Killer cells; Anti-tumor cytokine; Adoptive immunotherapy; Head and neck cancer; 頭頚部癌; 臨床免疫学; 脾臓細胞; キラ-細胞; 口腔癌

Culture of peripheral blood mononuclear cells(PBMC) with a heat and penicillin-treated streptococcal preparation, OK-432 has induced effector cells which have both cell-mediated and cytokine-mediated antitumor activities. The cell-mediated activities were attributed to natural killer(NK) cells and lymphokine activated killer(LAK) cells. The cytokine-mediated activities were mainly due to production of tumor growth inhibitory factor(TGIF), which was distinct from other cytokines and was synergize with IFN gamma. Frozen-stored human spleen cells cultured with OK-432(OK-SP) also acquired direct cytotoxicity to autologous as well as allogeneic tumor cells. The activated cells started to produce cytocidal cytokines such as TGIF and IFN gamma.These OK-MC and OK-SP were adoptively transferred into head and neck cancer patients in combination with chemotherapy and/or radiation therapy, and their therapeutic effects were examined. AIT was performed by intra-arterial or intratumoral administration of these cells. Of the 17 patients who received OK-MC, 6 of them(6/17 ; 35%) was obtained complete remission(CR) of the tumor, and partial remission(PR) was attained in 9 of the 17(9/17 ; 53%). Furthermore, complete disappearance of the tumor cells was observed in 4 of CR cases and 4 of the 9 PR patients. OK-SP were also injected into two cancer patients. In these patients, PR was obtained in one case and the other had MR with rapid necrosis of cancer tissue and remarkable decrease of tumor markers. There were no severe side effects. These results indicate the feasibility in using allogeneic spleen cells for adoptive local immunotherapy.

用热和青霉素处理的链球菌制剂培养外周血单个核细胞（PBMC），OK-432诱导了具有细胞介导和精氨酸介导的抗肿瘤活性的效应细胞。细胞介导的活性归因于自然杀伤（NK）细胞和淋巴因子激活的杀伤（LAK）细胞。干扰素介导的活性主要是由于肿瘤生长抑制因子（TGIF）的产生，TGIF与其他细胞因子不同，并与IFN γ有协同作用。用OK-432（OK-SP）培养的冷冻储存的人脾细胞也获得对自体以及同种异体肿瘤细胞的直接细胞毒性。活化细胞产生TGIF、IFN γ等细胞因子，将这些OK-MC、OK-SP过继转移到头颈癌患者体内，并与化疗和/或放疗联合应用，观察其治疗效果。通过动脉内或肿瘤内施用这些细胞进行AIT。OK-MC组17例，完全缓解6例（35%），部分缓解9例（53%）。此外，4例CR患者和4例PR患者中观察到肿瘤细胞完全消失。两名癌症患者也注射了OK-SP。在这些患者中，1例获得PR，另1例出现MR，癌组织迅速坏死，肿瘤标志物显著降低。没有严重的副作用。这些结果表明同种异体脾细胞用于过继性局部免疫治疗是可行的。

项目成果

Kubota Eiro: "Locoregional immunotherapy of head and neck cancer utilzing allogeneic spleen cell-a report of 2 cases" Biotherapy. 6. 175-182 (1993)

Kubota Eiro：“利用同种异体脾细胞进行头颈癌的局部免疫治疗——附2例报告”生物疗法。

Katano Mitsuo: "A possible cinical application of multicytokineーproducing cytotoxic mononuclear call(MCCM)therapy" BIOTHERAPY. 3. 373-379 (1991)

Katano Mitsuo：“产生多细胞因子的细胞毒性单核细胞 (MCCM) 疗法的可能的愤世嫉俗的应用”生物疗法 3. 373-379 (1991)。

Hu Zhao-Liang: "Effective induction of human NK cells with OK-432 and further augmentation of their cytolytic funcyion by rIL-2" Microbiol Immunol. 38(in press). (1994)

胡兆亮：“用 OK-432 有效诱导人 NK 细胞，并通过 rIL-2 进一步增强其细胞溶解功能”微生物免疫学。

Kubota Eiro: "Induction of anti-tumor activities in OK-432-stimulated peripheral blood mononuclear cell and their possible application for adoptive immunotherapy in oral cancer patients" Oral and Maxillo-Facial Surgry Proceedings of the 16th Congress of I

久保田荣郎：“OK-432刺激的外周血单核细胞的抗肿瘤活性的诱导及其在口腔癌患者过继性免疫治疗中的可能应用”第16届口腔颌面外科大会论文集

Nagumo F, Sano M, Tadano J, Katano M, Kubota E, Kikuchi M, and Nose Y.: "HLA-DP class II antigens in transfusion-associated graft versus host disease." Lancet. 342. 1424 (1993)

Nagumo F、Sano M、Tadano J、Katano M、Kubota E、Kikuchi M 和 Nose Y.：“输血相关移植物抗宿主病中的 HLA-DP II 类抗原。”