Adler A, Stein J A, Kedar E, Naor D, Weiss D W
J Biol Response Mod. 1984 Oct;3(5):491-500.
The clinical effect of intralesional injection of interleukin-2 (IL-2)-cultured autologous lymphocytes was assessed in seven patients with cutaneous, recurrent tumor nodules (12 melanoma and 8 mammary cancer lesions). Each tumor nodule was injected 3-10 times, once weekly, with IL-2-cultured lymphoid cells (CLC), 40-400 million cells at each injection. Lymphoid cells obtained from buffy coats were separated on Ficoll-Paque, cryopreserved in liquid nitrogen, thawed, and cultured for 1-2 weeks in the presence of crude IL-2 (containing phytohemagglutinin) before injection. CLC were tested for sterility, percent E-rosette-forming cells, and cytotoxicity against K562, allogeneic melanoma, and breast cancer cell lines and autologous tumor cells. Enhanced cytotoxicity was expressed by IL-2 CLC, as compared with nonstimulated peripheral blood lymphocytes (PBL). Arrest of tumor growth (compared with untreated lesions) was observed in eight lesions and partial regression in three lesions. Moreover, complete regression was noted in one large melanoma lesion treated with low-dose irradiation prior to intralesional administration of CLC and in three small intracutaneous melanoma lesions treated with CLC only. Histopathological findings of responding lesions showed infiltration with lymphoid cells and macrophages, with the tumor cells sparsely dispersed. No untoward side effects of CLC injections were observed. The present study points to the feasibility of trials of adoptive immunotherapy in cancer patients as indicated by the following: (a) response of lymphoid cells to IL-2 adequate--although reduced--in patients with metastatic disease, including those after chemo- or radiotherapy; (b) possibility of cryopreservation of PBL and repeated culturing in IL-2 after thawing, with cytotoxic activity unimpaired; (c) demonstrably enhanced cytotoxicity in vitro of IL-2 CLC; (d) demonstrable--although limited--clinical response to in situ treatments with IL-2 CLC; (e) good tolerance of treatment with CLC.
对7例有皮肤复发性肿瘤结节（12个黑色素瘤和8个乳腺癌病灶）的患者评估了病灶内注射白细胞介素-2（IL-2）培养的自体淋巴细胞的临床效果。每个肿瘤结节每周注射3 - 10次IL-2培养的淋巴细胞（CLC），每次注射4亿 - 40亿个细胞。从血沉棕黄层获得的淋巴细胞在Ficoll-Paque上分离，液氮冻存，解冻，并在注射前于粗制IL-2（含植物血凝素）存在的情况下培养1 - 2周。对CLC进行无菌、E花环形成细胞百分比以及对K562、同种异体黑色素瘤和乳腺癌细胞系及自体肿瘤细胞的细胞毒性检测。与未刺激的外周血淋巴细胞（PBL）相比，IL-2 CLC表现出增强的细胞毒性作用。观察到8个病灶的肿瘤生长停滞（与未治疗的病灶相比），3个病灶部分消退。此外，在病灶内注射CLC之前接受低剂量照射治疗的1个大黑色素瘤病灶以及仅接受CLC治疗的3个小皮内黑色素瘤病灶中观察到完全消退。有反应病灶的组织病理学结果显示有淋巴细胞和巨噬细胞浸润，肿瘤细胞稀疏分散。未观察到CLC注射的不良副作用。本研究表明癌症患者过继性免疫治疗试验具有可行性，依据如下：（a）转移性疾病患者（包括化疗或放疗后的患者）的淋巴细胞对IL-2有足够的反应——尽管有所降低；（b）PBL可冻存并解冻后在IL-2中反复培养，细胞毒性活性不受损害；（c）IL-2 CLC在体外有明显增强的细胞毒性；（d）对IL-2 CLC原位治疗有明显——尽管有限——的临床反应；（e）对CLC治疗耐受性良好。
