Ioannides C G, Fisk B, Jerome K R, Irimura T, Wharton J T, Finn O J
Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Immunol. 1993 Oct 1;151(7):3693-703.
CTL isolated from tumor infiltrating lymphocytes/tumor associated lymphocytes (TAL) infiltrating ovarian tumors have been demonstrated to mediate lysis of tumor targets after in vitro culture. These effector cells are of particular interest as cellular probes to detect and define human tumor Ag and epitopes that stimulate cellular immunity to human tumors. Polymorphic epithelial mucin (PEM) core peptides are potential candidates as tumor specific Ag because of their preferential expression on epithelial tumors. We report here that ovarian CTL-TAL can recognize mucin (Muc-1) core peptide of PEM. Several ovarian CTL-TAL lines were developed that recognized in a non-MHC restricted fashion an Muc-1+ ovarian tumor, but not Muc-1-tumor. To define the specificity of these CTL-TAL and exclude cross-reactivity with other potential Ag, cytotoxicity experiments were performed using as targets EBV-transformed cell lines with an expression construct containing the Muc.1 cDNA. These ovarian CTL-TAL lysed mucin core-peptide transfected cells but not targets transfected with an expression construct containing a mucin frame-shift mutant cDNA as control. In addition, targets pulsed with short synthetic peptides composed of amino acids 1-14 of the Muc 1 core peptide repeat were also lysed by the same CTL-TAL. This lysis was inhibited by the mAb SM3 that recognize an epitope on the mucin core peptide. These results, which are a demonstration of a specific Ag recognized by ovarian CTL-TAL, may be of interest for specific immunotherapy of ovarian cancer.
从浸润卵巢肿瘤的肿瘤浸润淋巴细胞/肿瘤相关淋巴细胞（TAL）中分离出的细胞毒性T淋巴细胞（CTL），经体外培养后已证明可介导对肿瘤靶标的裂解。作为细胞探针，这些效应细胞对于检测和定义刺激针对人类肿瘤的细胞免疫的人类肿瘤抗原（Ag）和表位尤为重要。多形性上皮粘蛋白（PEM）核心肽因其在上皮肿瘤上的优先表达而成为肿瘤特异性Ag的潜在候选物。我们在此报告，卵巢CTL-TAL可识别PEM的粘蛋白（Muc-1）核心肽。已建立了几种卵巢CTL-TAL细胞系，它们以非主要组织相容性复合体（MHC）限制的方式识别Muc-1 +卵巢肿瘤，而不识别Muc-1-肿瘤。为了确定这些CTL-TAL的特异性并排除与其他潜在Ag的交叉反应性，使用含有Muc.1 cDNA的表达构建体的EB病毒转化细胞系作为靶标进行了细胞毒性实验。这些卵巢CTL-TAL裂解了粘蛋白核心肽转染的细胞，但未裂解作为对照的用含有粘蛋白移码突变体cDNA的表达构建体转染的靶标。此外，用由Muc 1核心肽重复序列的氨基酸1-14组成的短合成肽脉冲处理的靶标也被相同的CTL-TAL裂解。这种裂解被识别粘蛋白核心肽上一个表位的单克隆抗体SM3抑制。这些结果证明了卵巢CTL-TAL识别的特异性Ag，可能对卵巢癌的特异性免疫治疗具有重要意义。
