Studies on Adoptive Immunotherapy Utilizing Allogeneic Spleen Cells Against Cancers

用高温和青霉素处理的链球菌制剂培养外周血单核细胞（PBMC）， OK-432诱导的效应细胞具有细胞介导和细胞因子介导的抗肿瘤活性。细胞介导的活性归因于自然杀伤细胞（NK）和淋巴因子激活杀伤细胞（LAK）。细胞因子介导的活性主要是由于肿瘤生长抑制因子（TGIF）的产生，TGIF不同于其他细胞因子，与IFN γ协同作用。用OK-432（OK-SP）培养的冷冻保存的人脾细胞也对自体和异体肿瘤细胞具有直接的细胞毒性。被激活的细胞开始产生细胞杀伤细胞因子，如tgf和IFN γ。将这些OK-MC和OK-SP联合化疗和/或放疗过继转移到头颈癌患者体内，观察其治疗效果。AIT是通过动脉内或肿瘤内给药这些细胞进行的。17例患者中，6例（6/17,35%）患者肿瘤完全缓解（CR）， 9例（9/17,53%）患者肿瘤部分缓解（PR）。4例CR患者和9例PR患者的肿瘤细胞完全消失。OK-SP也被注射到2名癌症患者体内。其中1例PR， 1例MR，癌组织快速坏死，肿瘤标志物明显降低。没有严重的副作用。这些结果提示异体脾细胞用于局部过继免疫治疗的可行性。

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.