Studies on Adoptive Immunotherapy Utilizing Allogeneic Spleen Cells Against Cancers

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。

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.