Tsang K Y, Zhu M, Nieroda C A, Correale P, Zaremba S, Hamilton J M, Cole D, Lam C, Schlom J
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-1750, USA.
Clin Cancer Res. 1997 Dec;3(12 Pt 1):2439-49.
CTL lines have now been generated against defined peptides of a range of human tumor-associated antigens (TAAs). One of the potential uses of these epitope-specific CTLs is in adoptive transfer immunotherapy. This is a modality, however, that will require long-term in vitro culture of CTLs. To date, little has been reported concerning the phenotypic stability of human epitope-specific CTLs as a consequence of long-term in vitro propagation via peptide stimulation. We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA). This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells. The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner. Vbeta T-cell receptor gene usage was also analyzed. These studies thus present a rationale for the use of long-term cultured epitope-specific human CTLs, directed against a human TAA for potential adoptive transfer immunotherapy protocols.
目前已针对一系列人类肿瘤相关抗原（TAA）的特定肽段产生了细胞毒性T淋巴细胞（CTL）系。这些表位特异性CTL的潜在用途之一是用于过继性转移免疫疗法。然而，这是一种需要对CTL进行长期体外培养的方法。迄今为止，关于通过肽刺激进行长期体外增殖后人类表位特异性CTL的表型稳定性，鲜有报道。我们在此报告了针对人癌胚抗原（CEA）的免疫显性表位（YLSGANLNL，命名为CAP-1）的CTL系的系列表型特征。该CTL系源自一名转移性癌患者的外周血单个核细胞，该患者在一项I期试验中接受了重组CEA-痘苗疫苗治疗；在自体抗原呈递细胞存在的情况下，用CAP-1肽和白细胞介素2对CTL进行20次体外刺激循环传代后进行分析。结果显示，该CTL系在细胞因子（干扰素-γ、肿瘤坏死因子和粒细胞-巨噬细胞集落刺激因子）高水平产生、归巢黏附分子表达、裂解肽脉冲靶标的能力以及以MHC限制方式裂解内源性表达CEA的人癌细胞的能力方面，表型稳定。还分析了VβT细胞受体基因的使用情况。因此，这些研究为使用针对人类TAA的长期培养的表位特异性人类CTL用于潜在的过继性转移免疫疗法方案提供了理论依据。
