INDUCTION OF ANTITUMOR CYTOTOXIC T-LYMPHOCYTES IN NORMAL HUMANS USING PRIMARY CULTURES AND SYNTHETIC PEPTIDE EPITOPES
INDUCTION OF ANTITUMOR CYTOTOXIC T-LYMPHOCYTES IN NORMAL HUMANS USING PRIMARY CULTURES AND SYNTHETIC PEPTIDE EPITOPES
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DOI：
10.1073/pnas.91.6.2105
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发表时间：
1994-03-15
影响因子：
11.1
通讯作者：
SERRA, HM
中科院分区：
文献类型：
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作者：
CELIS, E;TSAI, V;SERRA, HM
细胞毒性T淋巴细胞（CTL）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应答的肿瘤细胞衍生肽将使得能够设计抗原特异性免疫疗法。我们的策略，以确定这种潜在的治疗肽依赖于选择高亲和力的MHC结合剂从已知的肿瘤相关抗原。随后测试这些肽诱导能够杀死肿瘤细胞的CTL的能力。利用这种策略，我们已经鉴定了一个9个残基的表位，其来源于肿瘤相关基因法师-3的产物，其具有诱导体外CTL的能力，所述CTL杀死黑色素瘤和其他肿瘤细胞系。这些结果显示了肿瘤特异性人CTL的主要体外诱导，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。
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.