Immunotherapy of lymphomas with T cells modified by anti-CD20 scFv/CD28/CD3zeta recombinant gene

Leuk Lymphoma. 2008 Jul;49(7):1368-73. doi: 10.1080/10428190802064958.

Abstract

One of the approaches to make anti-CD20 antibody more efficient is to express this antibody on the surface of T cells. scFv from anti-CD20 antibody has been expressed on T cell surface to bind to CD20 positive cells and CD3zeta has been expressed as a fusion partner to transduct signals. T cells grafted with this chimeric scFv/CD3zeta were able to redirect grafted T cells to an MHC/Ag-independent antitumor response. To test the effects of CD28 signal on the cellular activation and antitumor effectiveness of chimeric scFv/CD3zeta modified T cells, we constructed a recombinant anti-CD20 scFv/CD28/CD3zeta gene in a retroviral vector. T cells expressing anti-CD20 scFv/CD28/CD3zeta specifically lysed CD20 positive target tumor cells and secreted not only IFN-gamma but also IL-2 after binding to their target cells. Our data indicate that CD3 and CD28 signalling can be delivered in one molecule, which is sufficient for complete T cell activation without exogenous B7/CD28 costimulation.

MeSH terms

  • Antigens, CD20 / immunology
  • CD28 Antigens / genetics
  • CD28 Antigens / therapeutic use
  • CD3 Complex / genetics
  • CD3 Complex / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Genetic Vectors
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / therapeutic use
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Lymphoma / therapy*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / therapeutic use*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transduction, Genetic

Substances

  • Antigens, CD20
  • CD28 Antigens
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Immunoglobulin Variable Region
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Interferon-gamma