Chikamatsu K, Reichert T E, Kashii Y, Saito T, Kawashiri S, Yamamoto E, Whiteside T L
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Int J Cancer. 1999 Aug 12;82(4):532-7. doi: 10.1002/(sici)1097-0215(19990812)82:4<532::aid-ijc11>3.0.co;2-g.
We have previously reported that immune anti-tumor effector cells, both cytotoxic T lymphocytes (CTLs) and IL-2-activated natural killer (A-NK) cells, are effective at eliminating human head-and-neck cancer (HNC) targets in vitro and in vivo in xenograft models. In this study, these 2 types of human effector cell were compared for the ability to prevent the development of lymph node metastases in a metastasis model of human squamous-cell carcinoma of the head and neck (SCCHN) established in nude mice. A tumor cell line, OSC-19, was injected into the floor of the mouth in nude mice, and the tumor grew progressively and metastasized to cervical lymph nodes by day 21. As effector cells, a human HLA-A2-restricted CTL line recognizing a shared antigen on OSC-19 and human non-MHC-restricted A-NK cells were used. Both types of effector cell mediated high levels of lysis against OSC-19 targets in 4-hr (51)Cr-release assays. Administration of human CTLs or A-NK cells and IL-2 to the site of tumor growth in mice with 7-day OSC-19 tumors resulted in significant reduction of the number of lymph node metastases relative to untreated or sham-operated controls or to mice treated with IL-2 without the effector cells. Our results suggest that in a xenograft model of human SCCHN implanted in the oral cavity of nude mice, the development of lymph node metastases can be successfully controlled by adoptive transfer of human SCCHN-specific CTLs or SCCHN-reactive A-NK cells plus IL-2.
我们之前曾报道，免疫抗肿瘤效应细胞，即细胞毒性T淋巴细胞（CTL）和白细胞介素-2激活的自然杀伤（A-NK）细胞，在体外和异种移植模型的体内均能有效消除人头颈部癌（HNC）靶点。在本研究中，比较了这两种人类效应细胞在裸鼠建立的人头颈部鳞状细胞癌（SCCHN）转移模型中预防淋巴结转移发生的能力。将肿瘤细胞系OSC-19注射到裸鼠的口腔底部，肿瘤逐渐生长，并在第21天转移至颈部淋巴结。作为效应细胞，使用了识别OSC-19上共享抗原的人类HLA-A2限制性CTL系和人类非MHC限制性A-NK细胞。在4小时的（51）铬释放试验中，这两种效应细胞均介导了对OSC-19靶点的高水平裂解。给患有7天OSC-19肿瘤的小鼠肿瘤生长部位注射人类CTL或A-NK细胞及白细胞介素-2，相对于未治疗或假手术对照组或仅用白细胞介素-2而无效应细胞治疗的小鼠，淋巴结转移数量显著减少。我们的结果表明，在植入裸鼠口腔的人类SCCHN异种移植模型中，通过过继转移人类SCCHN特异性CTL或SCCHN反应性A-NK细胞加白细胞介素-2，可以成功控制淋巴结转移的发生。
