Sacchi M, Snyderman C H, Heo D S, Johnson J T, d'Amico F, Herberman R B, Whiteside T L
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Cancer Res. 1990 May 15;50(10):3113-8.
The efficacy of local adoptive immunotherapy with human lymphokine-activated killer cells and recombinant interleukin 2 (rIL-2) in growth inhibition of established squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a nude mouse model. The model of xenografted SCCHN was established by s.c. injections of in vitro maintained tumor cells (2-10 x 10(6) cells/mouse) into the flank of splenectomized animals pretreated with cyclophosphamide (200 mg/kg). The SCCHN line used was tumorigenic in 95% of the appropriately conditioned nude mice. Inhibition of tumor growth by locally administered effector cells was the end point of the study, since the tumors did not metastasize within 6 weeks of tumor challenge. Either i.p. or local administration of rIL-2 alone (1000 units/day) to the tumor site daily for 2 weeks resulted in a significant inhibition of tumor growth. In the absence of detectable natural killer activity in these mice, a modest dose of rIL-2 had a direct antitumor effect on SCCHN cells in vivo. In addition, complete inhibition of tumor growth was achieved with 3 times weekly injections of 5-10 x 10(6) lymphokine-activated killer cells delivered to the tumor site and 1000 units of rIL-2 administered locally every day for 2 weeks. Our data indicate that local or systemic immunotherapy with rIL-2 alone or local adoptive immunotherapy with an adequate dose of lymphokine-activated killer cells plus rIL-2 may be effective in preventing the growth of established SCCHN tumors in vivo.
在裸鼠模型中评估了用人淋巴因子激活的杀伤细胞和重组白细胞介素2（rIL-2）进行局部过继免疫疗法对头颈部已确立的鳞状细胞癌（SCCHN）生长抑制的疗效。通过将体外培养的肿瘤细胞（2 - 10×10⁶个细胞/只小鼠）皮下注射到经环磷酰胺（200mg/kg）预处理的脾切除动物的胁腹，建立了异种移植SCCHN模型。所使用的SCCHN细胞系在95%经过适当条件处理的裸鼠中具有致瘤性。由于肿瘤在接种后6周内不发生转移，因此研究的终点是局部给予效应细胞对肿瘤生长的抑制作用。单独腹腔注射或局部给予rIL-2（1000单位/天）至肿瘤部位，持续2周，均导致肿瘤生长受到显著抑制。在这些小鼠中未检测到自然杀伤活性的情况下，适度剂量的rIL-2在体内对SCCHN细胞具有直接抗肿瘤作用。此外，每周3次向肿瘤部位注射5 - 10×10⁶个淋巴因子激活的杀伤细胞，并每天局部给予1000单位rIL-2，持续2周，可实现肿瘤生长的完全抑制。我们的数据表明，单独用rIL-2进行局部或全身免疫疗法，或用适当剂量的淋巴因子激活的杀伤细胞加rIL-2进行局部过继免疫疗法，可能有效地预防体内已确立的SCCHN肿瘤的生长。
