Xue B H, Zhang Y, Sosman J A, Peace D J
Department of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Prostate. 1997 Feb 1;30(2):73-8. doi: 10.1002/(sici)1097-0045(19970201)30:2<73::aid-pros1>3.0.co;2-l.
Prostate-specific antigen (PSA), a tissue-specific protein expressed by most adenocarcinomas of the prostate, might be a useful target for T-cell-mediated immunotherapy of prostate cancers. The current study examined whether it is possible to elicit human cytotoxic T lymphocytes (CTL) with specificity for PSA. A synthetic nonamer peptide, corresponding to residues 146-154 of PSA and containing a canonical HLA-A2-binding motif, was shown to stabilize the expression of HLA-A2 on the T2 antigen-processing mutant cell line. Repeated in vitro stimulation of peripheral blood lymphocytes from a normal HLA-A2+ donor induced CTL with specificity for the PSA 146-154 peptide. The peptide-induced CTL expressed the CD4- CD8+ cell surface phenotype and were restricted by HLA-A2. A large portion of patients with prostate cancer express the HLA-A2 phenotype, implying that many prostate cancers might be targeted by HLA-A2-restricted CTL with specificity for the PSA 146-154 epitope.
前列腺特异性抗原(PSA)是一种由大多数前列腺腺癌表达的组织特异性蛋白,可能是前列腺癌T细胞介导免疫治疗的一个有用靶点。当前研究检测了是否有可能诱导出对PSA具有特异性的人细胞毒性T淋巴细胞(CTL)。一种合成九肽,对应于PSA的146 - 154位氨基酸残基且包含一个典型的HLA - A2结合基序,已显示能稳定T2抗原加工突变细胞系上HLA - A2的表达。对一名正常HLA - A2 +供体的外周血淋巴细胞进行反复体外刺激,诱导出了对PSA 146 - 154肽具有特异性的CTL。该肽诱导的CTL表达CD4 - CD8 +细胞表面表型,并受HLA - A2限制。很大一部分前列腺癌患者表达HLA - A2表型,这意味着许多前列腺癌可能会被对PSA 146 - 154表位具有特异性的HLA - A2限制的CTL靶向。