Celis E, Tsai V, Crimi C, DeMars R, Wentworth P A, Chesnut R W, Grey H M, Sette A, Serra H M
Cytel, San Diego, CA 92121.
Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2105-9. doi: 10.1073/pnas.91.6.2105.
Cytotoxic T lymphocytes (CTLs) recognize peptide antigens associated with cell surface major histocompatibility complex (MHC) molecules. The identification of tumor cell-derived peptides capable of eliciting anti-tumor CTL responses would enable the design of antigen-specific immunotherapies. Our strategy to identify such potentially therapeutic peptides relies on selecting high-affinity MHC binders from known tumor-associated antigens. These peptides are subsequently tested for their ability to induce CTLs capable of killing tumor cells. With this strategy, we have identified a nine-residue epitope, derived from the product of the tumor-associated gene MAGE-3, which has the capacity to induce in vitro CTLs that kill melanoma and other tumor cell lines. These results show the primary in vitro induction of tumor-specific human CTLs and illustrate the feasibility of ex vivo antigen-specific approaches to the immunological therapy of cancer.
细胞毒性T淋巴细胞（CTLs）识别与细胞表面主要组织相容性复合体（MHC）分子相关的肽抗原。鉴定能够引发抗肿瘤CTL反应的肿瘤细胞衍生肽将有助于设计抗原特异性免疫疗法。我们识别此类潜在治疗性肽的策略依赖于从已知肿瘤相关抗原中选择高亲和力MHC结合物。随后测试这些肽诱导能够杀死肿瘤细胞的CTLs的能力。通过这种策略，我们鉴定出了一种源自肿瘤相关基因MAGE - 3产物的九肽表位，它有能力在体外诱导杀死黑色素瘤和其他肿瘤细胞系的CTLs。这些结果显示了肿瘤特异性人CTLs的初步体外诱导，并说明了离体抗原特异性方法用于癌症免疫治疗的可行性。
