title: Adoptive antitumor immunotherapy in vitro and in vivo using genetically activated erbB2-specific T cells.
abstract: The use of human T lymphocytes genetically modified to express chimeric antigen receptors on their surfaces has emerged as a promising treatment strategy for malignant tumors. We have transfected primary human peripheral T lymphocytes with a recombinant vector carrying DNA fragments encoding anti-erbB2 scFv/Fc/CD28/CD3ζ chimeric antigen receptor using electroporation. Transfected T cells have been demonstrated to express anti-erB2 scFv/Fc on their surface and CD28/CD3ζ intracellularly. These modified T cells were able to specifically bind to erbB2 tumor-associated antigen on target tumor cells. After specific binding, modified T cells were activated to produce high levels of cytokines (not only interferon-γ but also interluekin-2) and mediate lysis of erbB2-positive human tumor cells in an antigen-specific manner. Furthermore, such genetically modified human T cells significantly delayed the growth of subcutaneous erbB2-positive human xenograft tumors after systemic administration. These preclinical studies suggest that human T cells can be modified genetically and redirected to tumors in cancer patients.
authors: *Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Science ‡The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang †Xuanwu Hospital, Capital Medical University, Beijing, P.R. China.
authors: Chaoyan
authors: C
authors: Wang
authors: Wangxiong
authors: W
authors: Hu
authors: Luxi
authors: L
authors: Shen
authors: Ruiyan
authors: R
authors: Dou
authors: Shengke
authors: S
authors: Zhao
authors: Daming
authors: D
authors: Shan
authors: Kang
authors: K
authors: Yu
authors: Rong
authors: R
authors: Huang
authors: Hongzhi
authors: H
authors: Li
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018274:Electroporation; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins