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: Chaoyan Wang, Wangxiong Hu, Luxi Shen, Ruiyan Dou, Shengke Zhao, Daming Shan, Kang Yu, Rong Huang, Hongzhi Li
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 37 Issue 7 Pg. 351-9 (Sep 2014) ISSN: 1537-4513 [Electronic] United States
• PMID: 25075564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD28 Antigens
• CD3 Complex
• Recombinant Fusion Proteins
• Receptor, ErbB-2

Topics

• Animals
• CD28 Antigens (genetics, immunology)
• CD3 Complex (genetics, immunology)
• Cell Line, Tumor
• Disease Models, Animal
• Electroporation
• Gene Expression
• Genetic Therapy
• Humans
• Immunohistochemistry
• Immunotherapy, Adoptive
• Lymphocyte Activation (immunology)
• Neoplasms (genetics, immunology, pathology, therapy)
• Receptor, ErbB-2 (genetics, immunology, metabolism)
• Recombinant Fusion Proteins (genetics, immunology)
• T-Cell Antigen Receptor Specificity (immunology)
• T-Lymphocytes (immunology, metabolism)
• Transfection
• Tumor Burden
• Xenograft Model Antitumor Assays