Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads to a functionally heterogeneous CTL response
Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads to a functionally heterogeneous CTL response
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DOI：
10.1097/00002371-199907000-00002
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发表时间：
1999-07-01
影响因子：
3.9
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
--
作者：
Dudley, ME;Nishimura, MI;Rosenberg, SA
使用肽抗原进行主动疫苗接种和转移性癌症患者治疗的实验性临床方案的目标是诱导针对免疫抗原的强烈细胞毒性T淋巴细胞（CTL）反应，从而对抗表达抗原的肿瘤细胞。然而，由肽免疫诱导的人类CTL反应的强度和广度，特别是针对正常组织和肿瘤表达的抗原，并没有很好地表征。这一问题是通过对三名接受肽免疫治疗的转移性黑色素瘤患者外周血单个核细胞的CTL样细胞进行表征来研究的。所有患者均接受G9-209-2M肽治疗，这是一种gp100黑色素瘤相关抗原的修饰表位。结果表明，该肽抗原诱导的CTL反应在对肽抗原的亲切性和对肿瘤细胞系的识别方面具有高度的异质性。此外，每种CTL cloid对天然肽的亲和力可以高度预测肿瘤的反应性。这些结果在他们的肽类疫苗接种和过继性肿瘤免疫治疗的意义方面进行了讨论。
The goal of experimental clinical protocols using peptide antigen for active vaccination and treatment of patients with metastatic cancer is to induce a vigorous cytotoxic T lymphocyte (CTL) response against the immunizing antigen, and thereby against tumor cells expressing the antigen. However, the magnitude and breadth of human CTL responses induced by peptide immunization, and in particular against antigens expressed by normal tissues as well as tumors, is not well characterized. This issue was examined by characterizing CTL cloids derived from peripheral blood mononuclear cells of three patients who received peptide immunization as treatment for metastatic melanoma. All patients received G9-209-2M peptide, a modified epitope of the gp100 melanoma-associated antigen. The results indicated that the CTL response induced by this peptide antigen was highly heterogeneous both in terms of avidity toward the peptide antigen and recognition of tumor cell lines. Furthermore, avidity of each CTL cloid for the native peptide was highly predictive of tumor reactivity. These results are discussed in terms of their implications for peptide vaccination and adoptive tumor immunotherapy.