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.