Sadeghi N, Black M J, Hier M P, Shenouda G, Karp S E
Department of Otolaryngology, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec.
Arch Otolaryngol Head Neck Surg. 1997 Jan;123(1):25-30. doi: 10.1001/archotol.1997.01900010029004.
To study immunotherapy for advanced head and neck squamous cell carcinoma using AT-84, a spontaneously arising murine tumor. We examined the draining lymph nodes (DLNs) for generation of potential therapeutic lymphocytes in head and neck squamous cell carcinoma.
Experimental randomized control trial.
Therapeutic T cells from DLNs were generated by the sequential activation of the in vivo-primed DLN cells with 2C11, and anti-CD3 antibody, and interleukin-2 (IL-2). Immunotherapy of mice bearing lung metastases was carried out in various experiments with low-dose systemic IL-2 and activated DLN cells. Using a 4-hour radioactive chromium Cr 51 release assay, in vitro cytotoxicity of these cells also was examined.
Mice immunized with this tumor failed to reject the growth of a subsequent challenge with the tumor. Immunotherapy with low-dose systemic IL-2 resulted in a mean reduction of 79% in the number of lung metastases. Adoptive immunotherapy with activated DLN cells was effective in all experiments, with a mean reduction of 59% in the number of metastases in immunodeficient mice. However, DLN cells were not directly cytotoxic to the tumor cells in in vitro assays, unlike control lymphokine-activated killer cells.
AT-84 is a nonimmunogenic tumor similar to many human malignant neoplasms, making this a suitable model for immunotherapy. Low-dose systemic IL-2 was effective in reduction of established metastasis in this model. Activated DLN cells show reproducible in vivo therapeutic efficacy despite lack of in vitro cytotoxicity. Use of DLN cells as sources of therapeutic T cells in patients with head and neck squamous cell carcinoma deserves exploration because they are readily obtainable and because conventional treatment is of limited benefit.
利用自发产生的小鼠肿瘤AT - 84研究晚期头颈部鳞状细胞癌的免疫疗法。我们对头颈部鳞状细胞癌引流淋巴结（DLN）中潜在治疗性淋巴细胞的生成进行了检测。
实验性随机对照试验。
通过用2C11、抗CD3抗体和白细胞介素-2（IL - 2）依次激活体内致敏的DLN细胞来产生来自DLN的治疗性T细胞。在各种实验中，对患有肺转移的小鼠进行低剂量全身IL - 2和活化的DLN细胞的免疫治疗。使用4小时放射性铬Cr 51释放试验，还检测了这些细胞的体外细胞毒性。
用该肿瘤免疫的小鼠未能排斥随后肿瘤攻击的生长。低剂量全身IL - 2免疫治疗使肺转移灶数量平均减少79%。在所有实验中，用活化的DLN细胞进行过继性免疫治疗均有效，免疫缺陷小鼠转移灶数量平均减少59%。然而，与对照淋巴因子激活的杀伤细胞不同，在体外试验中DLN细胞对肿瘤细胞没有直接细胞毒性。
AT - 84是一种与许多人类恶性肿瘤相似的非免疫原性肿瘤，使其成为免疫疗法的合适模型。低剂量全身IL - 2在该模型中对减少已形成的转移有效。尽管缺乏体外细胞毒性，但活化的DLN细胞在体内显示出可重复的治疗效果。将DLN细胞用作头颈部鳞状细胞癌患者治疗性T细胞的来源值得探索，因为它们易于获得且传统治疗的益处有限。
