Brouwenstijn N, Hoogstraten C, Verdegaal E M, Van der Spek C W, Deckers J G, Mulder A, Osanto S, Schrier P I
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
J Immunother. 1998 Nov;21(6):427-34. doi: 10.1097/00002371-199811000-00004.
From peripheral blood mononuclear cells of a patient with renal cell carcinoma (RCC), we isolated several T-cell clones, which efficiently lyse the autologous RCC cell line (LE-8915-RCC), but not the autologous Epstein Barr virus-transformed lymphoblastoid cell line. Most of the cytotoxic T lymphocyte (CTL) clones recognize HLA-A1-positive allogeneic RCC cell lines, indicating that HLA-A1 is the restricting element for these T cells. One CTL clone exclusively recognizes the autologous tumor cells. The HLA-A1-restricted CTL clones can be divided further into two subsets of T-cell clones, one blocked by an HLA-A1-specific monoclonal antibody, the other not. The reactivity of HLA-A1-restricted T-cell clone 6/135 was studied in greater detail. This T-cell clone also recognizes a number of melanoma cell lines, indicating that expression of the antigen seen by this CTL clone is not restricted to RCC. Strikingly, the antigen is not exclusively expressed by tumor cell lines, because primary cultures of proximal tubulus epithelium cells, adult mesangial cells, and normal breast epithelium cells are also lysed. These results corroborate the notion that renal carcinoma cells are immunogenic by virtue of a broadly distributed antigenic structure that may serve as a target for cytotoxic T cells and may be a potential candidate for tumor vaccine development.
从一名肾细胞癌(RCC)患者的外周血单个核细胞中,我们分离出了几个T细胞克隆,这些克隆能有效地裂解自体RCC细胞系(LE - 8915 - RCC),但不能裂解自体爱泼斯坦 - 巴尔病毒转化的淋巴母细胞系。大多数细胞毒性T淋巴细胞(CTL)克隆识别HLA - A1阳性的同种异体RCC细胞系,这表明HLA - A1是这些T细胞的限制元件。一个CTL克隆专门识别自体肿瘤细胞。HLA - A1限制的CTL克隆可进一步分为两个T细胞克隆亚群,一个被HLA - A1特异性单克隆抗体阻断,另一个则不受影响。我们更详细地研究了HLA - A1限制的T细胞克隆6/135的反应性。这个T细胞克隆还识别一些黑色素瘤细胞系,这表明该CTL克隆所识别的抗原的表达并不局限于RCC。引人注目的是,该抗原并非仅由肿瘤细胞系表达,因为近端肾小管上皮细胞、成人系膜细胞和正常乳腺上皮细胞的原代培养物也会被裂解。这些结果证实了这样一种观点,即肾癌细胞具有免疫原性,这得益于一种广泛分布的抗原结构,该结构可能作为细胞毒性T细胞的靶标,并且可能是肿瘤疫苗开发的潜在候选物。