Immunotherapy of lymphomas with T cells modified by anti-CD20 scFv/CD28/CD3zeta recombinant gene.
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.
Yu
Kang
K
Department of Hematology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
Hu
Yongxian
Y
Tan
Yinxia
Y
Shen
Zhijian
Z
Jiang
Songfu
S
Qian
Honglan
H
Liang
Bin
B
Shan
Daming
D
D018951:Antigens, CD20 / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000627:therapeutic use; D017252:CD3 Complex / Q000235:genetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008223:Lymphoma / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic
D018951:Antigens, CD20; D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D007135:Immunoglobulin Variable Region; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma