Bukowski R M, Sharfman W, Murthy S, Rayman P, Tubbs R, Alexander J, Budd G T, Sergi J S, Bauer L, Gibson V
Department of Experimental Therapeutics, Cleveland Clinic, Ohio 44195-5236.
Cancer Res. 1991 Aug 15;51(16):4199-205.
A Phase I trial of tumor-infiltrating lymphocytes (TIL) expanded in vitro and administered on Days 1 and 8, with or without continuous infusion recombinant interleukin 2 (rIL-2) in 25 patients with metastatic renal cell carcinoma, was conducted. Eighteen of the 25 eligible patients were treated with TIL and escalating doses of rIL-2 (0.0, 3.0, 4.5 x 10(6) units/m2) on Days 1 to 5 and 8 to 12. Dose-limiting toxicity was pulmonary, and the maximum tolerated dose of rIL-2 was 3.0 x 10(6) units/m2. No clinical responses were observed. Immunological monitoring of peripheral blood lymphocytes demonstrated significant increases in CD3+ and CD56+ cells, including the activated T-cell subsets. Phenotypic analysis of cultured TILs demonstrated significant heterogeneity and the presence of CD3+CD4+ and CD3+CD8+ T-cells, with CD3-CD56+ and CD3+CD56+ populations also present. The majority of cultured TILs expressed HLA-DR and CD45RO, with a variable number expressing CD25. The rIL-2-expanded TILs possessed cytotoxicity against allogeneic and autologous tumor, with cytolytic activity against only autologous tumor seen in one patient. Results demonstrate that in vitro expansion of TILs is possible, but further studies are needed to define the biology of TILs in renal cancer and to isolate and expand tumor-specific T-cells.
开展了一项针对25例转移性肾细胞癌患者的I期试验，对体外扩增的肿瘤浸润淋巴细胞（TIL）于第1天和第8天进行给药，同时给予或不给予持续输注重组白细胞介素2（rIL-2）。25例符合条件的患者中有18例接受了TIL治疗，并在第1至5天和第8至12天给予递增剂量的rIL-2（0.0、3.0、4.5×10⁶单位/m²）。剂量限制性毒性为肺部毒性，rIL-2的最大耐受剂量为3.0×10⁶单位/m²。未观察到临床反应。对外周血淋巴细胞的免疫监测显示CD3⁺和CD56⁺细胞显著增加，包括活化的T细胞亚群。对培养的TIL进行表型分析显示存在显著的异质性，存在CD3⁺CD4⁺和CD3⁺CD8⁺T细胞，也存在CD3⁻CD56⁺和CD3⁺CD56⁺群体。大多数培养的TIL表达HLA-DR和CD45RO，少数表达CD25。rIL-2扩增的TIL对同种异体和自体肿瘤具有细胞毒性，仅在1例患者中观察到对自体肿瘤的溶细胞活性。结果表明，TIL的体外扩增是可行的，但需要进一步研究来确定肾癌中TIL的生物学特性，并分离和扩增肿瘤特异性T细胞。
