新型胃癌特异的嵌合锚定T细胞构建及杀伤活性研究

According to the co-stimulatory signal theory and the latest development of anchored-T cell research, we design a new genetic strategy to target CD28-mediated costimulation in an antigen-specific manner. The single-chain antibody variable fragments (scFv) are cloned from hybridoma cells against gastric cancer established in our laboratory or from antibody library constructed using phage-display method. Next, we construct several chimeric molecules, which consist of a single-chain antibody (scFv) binding domain specific against tumor derived from gastroinstestinal adenocarcinomas and the transmembrane and intracellular domain of either CD3 zeta or CD28 signaling chain. Results show the expressed proteins retain both antigen-binding properties of antibody and cytokine associated functions. Through lipid transfection, we successfully establish antigen-specific cytotoxic T cells. Upon co-culture with antigen-positive tumor cells, chimeric molecule-grafted T cells are specifically and efficiently activated to cytolysis and cytokine secretion. In addition, in animals bearing tumors, fusion proteins are able to target the tumor and to elicit significant anti-tumor responses that result in reduced tumor size and prolonged living time of naked mice. In summary, in this work, we establish a novel anchored-T cell immuno-therapy pathway against gastroinstestinal adenocarcinomas and the results demonstrate its feasibility for clinical application.

依据肿瘤免疫双信号学说及锚定T细胞研究进展，以我所已建立的胃癌单克隆抗体系形。τ没蚬こ碳际豕菇∕G胃癌单克隆抗体与CD28和CD3ζ分子的嵌合分子scFv-CD28、scFv-CD3ζ，经体外转导T细胞，建立胃癌特异的嵌合锚定T细胞免疫疗法；观察体内、馍鄙诵裕冉锨逗戏肿痈髯宰饔眉傲闲вΓ范ㄉ绷鲂Ч俅灿τ玫於ㄊ笛榛