Immunotherapy of lymphomas with T cells modified by anti-CD20 scFv/CD28/CD3ζ recombinant gene

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 CD3ζ has been expressed as a fusion partner to transduct signals. T cells grafted with this chimeric scFv/CD3ζ 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/CD3ζ modified T cells, we constructed a recombinant anti-CD20 scFv/CD28/CD3ζ gene in a retroviral vector. T cells expressing anti-CD20 scFv/CD28/CD3ζ specifically lysed CD20 positive target tumor cells and secreted not only IFN-γ 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.

Keywords:

• Cellular immunotherapy
• anti-CD20 antibody
• CD3
• CD28
• scFv
• lymphoma