Horváth J, Szabó-Szabari M, Sinkovics J G
Saint Joseph's Hospital, Department of Medicine, Tampa, Florida 33607.
Acta Microbiol Immunol Hung. 1994;41(2):205-14.
In the authors' institution patients suffering from metastatic melanoma, renal cell carcinoma or mesothelioma, resistant to conventional therapeutic modilities, are treated with adoptive immunotherapy. Tumour infiltrating lymphocytes (TIL) are prepared from surgical samples and expanded ex vivo in the presence of recombinant interleukin-2 (rIL-2). When sufficient amount of cells are available (5 x 10(9)-10(10)) they are being reinfused. The patients also receive rIL-2 subcutaneously to support the activity and proliferation of reinfused TIL, and to avoid side effects caused by bolus or continuous intravenous administration. Leukapheresed lymphocytes activated by conditioned medium from OKT3 stimulated autologous lymphocytes and rIL-2 (autologous activated lymphocytes, AAL) are used as an alternative when TIL is not available or until it can be produced in sufficient amount. Subcutaneous IL-2 and oral cimetidine are also administered to support the reinfused AAL and to inhibit activation of CD8+ suppressor cells, respectively. Expression of activation markers CD25 and HLA-DR are monitored by flow cytometry as well as cytotoxicity is measured against K562 (NK specific target), HeLa (AALT specific) and against allogeneic or autologous tumour cell targets with a non-radioactive test. Methods are discussed by which the therapeutic efficiency of infused lymphocyte preparations can be improved.
在作者所在机构，转移性黑色素瘤、肾细胞癌或间皮瘤患者若对传统治疗方法耐药，则接受过继性免疫治疗。肿瘤浸润淋巴细胞（TIL）从手术样本中制备，并在重组白细胞介素-2（rIL-2）存在的情况下在体外扩增。当有足够数量的细胞（5×10⁹ - 10¹⁰）时，将其回输。患者还皮下注射rIL-2，以支持回输的TIL的活性和增殖，并避免大剂量或持续静脉给药引起的副作用。当无法获得TIL或直至能制备出足够数量的TIL时，可用经OKT3刺激的自体淋巴细胞和rIL-2的条件培养基激活的白细胞分离淋巴细胞（自体激活淋巴细胞，AAL）作为替代。皮下注射IL-2和口服西咪替丁，分别用于支持回输的AAL和抑制CD8⁺抑制细胞的激活。通过流式细胞术监测激活标志物CD25和HLA-DR的表达，并通过非放射性试验测定对K562（NK特异性靶标）、HeLa（AALT特异性）以及同种异体或自体肿瘤细胞靶标的细胞毒性。文中讨论了提高输注淋巴细胞制剂治疗效果的方法。
