Peoples G E, Smith R C, Linehan D C, Yoshino I, Goedegebuure P S, Eberlein T J
Laboratory of Biological Cancer Therapy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell Immunol. 1995 Sep;164(2):279-86. doi: 10.1006/cimm.1995.1171.
We have previously shown the importance of human leukocyte antigen (HLA)-A2 and the proto-oncogene HER2/neu in the T cell recognition of ovarian cancer. Since these proteins are ubiquitously expressed in epithelial-derived tumors, we have acid-eluted HLA-bound peptides from ovarian cancers, fractionated the peptides, and reconstituted T cell epitopes on the HLA-A2+ T2 cell line to determine if common tumor-associated antigens exist among HLA-A2+, HER2/neu+ epithelial cancers. We demonstrate that tumor-specific cytotoxic T lymphocytes (CTL) generated from tumor-infiltrating lymphocytes isolated from three ovarian, two breast, and two non-small-cell lung cancers recognize at least three of the same peptide fractions from multiple elutions. One of these peptide fractions coelutes with a HER2/neu-derived peptide which has been shown recently to be recognized by these same CTL. These findings demonstrate that a common peptide-based tumor vaccine is theoretically possible for many different epithelial-derived cancers.
我们之前已经证明了人类白细胞抗原(HLA)-A2和原癌基因HER2/neu在卵巢癌T细胞识别中的重要性。由于这些蛋白质在上皮来源的肿瘤中普遍表达,我们从卵巢癌中酸洗脱HLA结合肽,对肽进行分级分离,并在HLA-A2+ T2细胞系上重建T细胞表位,以确定在HLA-A2+、HER2/neu+上皮癌中是否存在常见的肿瘤相关抗原。我们证明,从3例卵巢癌、2例乳腺癌和2例非小细胞肺癌中分离的肿瘤浸润淋巴细胞产生的肿瘤特异性细胞毒性T淋巴细胞(CTL)识别多次洗脱中至少三种相同的肽级分。这些肽级分中的一种与一种HER2/neu衍生肽共洗脱,最近已证明这些相同的CTL可识别该肽。这些发现表明,理论上针对许多不同上皮来源癌症的基于肽的通用肿瘤疫苗是可行的。