Tuttle T M, Bethke K P, Inge T H, McCrady C W, Pettit G R, Bear H D
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Surg Res. 1992 Jun;52(6):543-8. doi: 10.1016/0022-4804(92)90126-k.
Adoptive immunotherapy in humans may be limited by the lack of autologous tumor cells to activate and expand tumor-specific T cells. Pharmacologic manipulation of protein kinase C (PKC) and intracellular calcium may substitute for tumor antigen and stimulate T cells for adoptive immunotherapy. In the present study, we evaluated the ability of the PKC activator Bryostatin 1 (B) plus the calcium ionophore ionomycin (I) to activate lymphocytes obtained from popliteal lymph nodes (DLN) draining an MCA-105 footpad tumor. The adoptive transfer of B/I-stimulated DLN cells eradicated MCA-105 pulmonary metastases. These lymphocytes do not require concomitant IL-2 administration to mediate regression of lung metastases. Three days after intrasplenic injection of tumor cells and splenectomy, mice were given iv injections of B/I-stimulated DLN cells. Adoptive immunotherapy with these cells induced regression of established liver metastases. In an intradermal tumor model, the adoptive transfer of B/I-stimulated MCA-105 DLN cells cured mice of MCA-105 intradermal (id) tumors, but did not induce regression of MCA-206 tumors. Mice cured of MCA-105 id tumors were protected against MCA-105, but not MCA-203, tumor challenge in the footpad 7 weeks after adoptive immunotherapy.
人类的过继性免疫疗法可能会受到缺乏自体肿瘤细胞来激活和扩增肿瘤特异性T细胞的限制。蛋白激酶C（PKC）和细胞内钙的药理学操作可能替代肿瘤抗原并刺激T细胞用于过继性免疫疗法。在本研究中，我们评估了PKC激活剂苔藓抑素1（B）加钙离子载体离子霉素（I）激活从引流MCA - 105足垫肿瘤的腘淋巴结（DLN）获得的淋巴细胞的能力。B/I刺激的DLN细胞的过继性转移消除了MCA - 105肺转移灶。这些淋巴细胞介导肺转移灶消退不需要同时给予白细胞介素-2。在脾内注射肿瘤细胞和脾切除术后三天，给小鼠静脉注射B/I刺激的DLN细胞。用这些细胞进行过继性免疫疗法可诱导已形成的肝转移灶消退。在皮内肿瘤模型中，B/I刺激的MCA - 105 DLN细胞的过继性转移治愈了患有MCA - 105皮内（id）肿瘤的小鼠，但未诱导MCA - 206肿瘤消退。过继性免疫疗法7周后，治愈了MCA - 105 id肿瘤的小鼠对足垫中的MCA - 105肿瘤攻击有保护作用，但对MCA - 203没有。
