Dudley M E, Ngo L T, Westwood J, Wunderlich J R, Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA.
Cancer J. 2000 Mar-Apr;6(2):69-77.
The modified peptide epitope gp100:209-217 (210M), referred to as g209-2M, of the gp100 melanocyte differentiation protein, when administered to melanoma patients by subcutaneous injection in incomplete Freund's adjuvant, is capable of generating HLA-A2-restricted CD8+ lymphocytes that specifically recognize the native gp100:209-217 (g209) peptide as well as gp100-expressing tumor cells. To evaluate the suitability of cloned lymphocytes from immunized patients for use in adoptive transfer therapy protocols, the functional and phenotypic variation of individual CD8+ T cell clones comprising the antitumor immune response was evaluated.
T-cell clones from melanoma patients who received g209-2M immunization were isolated and expanded, and their specific antitumor functional phenotypes were characterized.
g209-specific CD8+ lymphocytes that specifically recognized gp100-expressing tumor cells were readily obtained from g209-2M-immunized patients. There was substantial variation in the absolute levels of cytokine secretion and target cell lysis by g209-specific clones from each patient. Furthermore, individual clones demonstrated discordant secretion of different proinflammatory cytokines. These clonal phenotypes were stable, even after large expansions in cell number.
These results indicate that g209-2M peptide immunization of melanoma patients leads to a functionally diverse population of T cells, many of which are capable of expansion ex vivo to cell numbers appropriate for adoptive immunotherapy. However, the selection of a particular antigen-specific T-cell clone for treatment should be based on multiple functional criteria.
黑色素细胞分化蛋白gp100的修饰肽表位gp100:209 - 217（210M），称为g209 - 2M，当在不完全弗氏佐剂中通过皮下注射给予黑色素瘤患者时，能够产生HLA - A2限制性CD8 +淋巴细胞，这些淋巴细胞能够特异性识别天然gp100:209 - 217（g209）肽以及表达gp100的肿瘤细胞。为了评估来自免疫患者的克隆淋巴细胞在过继转移治疗方案中的适用性，对构成抗肿瘤免疫反应的单个CD8 + T细胞克隆的功能和表型变异进行了评估。
分离并扩增接受g209 - 2M免疫的黑色素瘤患者的T细胞克隆，并对其特异性抗肿瘤功能表型进行表征。
从接受g209 - 2M免疫的患者中很容易获得特异性识别表达gp100的肿瘤细胞的g209特异性CD8 +淋巴细胞。每位患者的g209特异性克隆在细胞因子分泌的绝对水平和靶细胞裂解方面存在很大差异。此外，单个克隆表现出不同促炎细胞因子的不一致分泌。即使在细胞数量大量扩增后，这些克隆表型仍然稳定。
这些结果表明，黑色素瘤患者的g209 - 2M肽免疫导致功能多样的T细胞群体，其中许多细胞能够在体外扩增至适合过继免疫治疗的细胞数量。然而，选择特定的抗原特异性T细胞克隆进行治疗应基于多种功能标准。
