Kim D K, Lee T V, Castilleja A, Anderson B W, Peoples G E, Kudelka A P, Murray J L, Sittisomwong T, Wharton J T, Kim J W, Ioannides C G
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77035, USA.
Anticancer Res. 1999 Jul-Aug;19(4B):2907-16.
Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.
从在含白细胞介素-2的培养基中培养的恶性腹水中分离出的肿瘤相关淋巴细胞（TAL）显示出抗肿瘤反应。这些抗肿瘤反应由细胞毒性T淋巴细胞（CTL）介导，CTL利用T细胞受体在MHC分子的背景下识别抗原。CD8 + CTL在MHC I类分子的背景下识别从细胞蛋白加工而来的肽表位。这些肽的长度限制为8 - 11个氨基酸。叶酸结合蛋白（FBP）在90%以上的卵巢癌和20 - 50%的乳腺癌中过度表达。我们最近发现FBP是许多这些CTL - TAL识别的抗原肽的来源。这表明FBP肽在体内对卵巢和乳腺CTL - TAL具有抗原性。为了确定FBP的免疫原性，通过CD14方法从健康供体分离的外周血单核细胞（PBMC）来源的树突状细胞（DC）将定义表位E39（FBP，191 - 199）的肽呈递给卵巢和乳腺CTL - TAL。在IL - 2存在的情况下，用E39脉冲DC（DC - E39）刺激卵巢和乳腺CTL - TAL，可迅速增强或诱导E39特异性CTL活性。基于DC - E39与DC - NP刺激的TAL中这些家族百分比的增加，这个E39反应群体由表达TCR Vβ9、Vβ13和Vβ17家族的细胞组成。免疫原性肿瘤抗原的表征以及诱导功能性抗肿瘤效应器所需的细胞因子的表征对于未来癌症疫苗的开发可能很重要。
