Tumor-specific T-bodies: towards clinical application.
Unlike antibodies, T cells are well suited to penetrate and destroy solid tumors. The T-body approach combines antibody recognition and T cells effector function. It is based on T cells expressing chimeric receptors composed of antibody-derived Fv or scFv as their extracellular recognition elements joined to lymphocyte triggering molecules. This receptors can redirect the specificity of T cells in an MHC independent manner. Upon encountering their target cells, T-bodies are able to undergo specific stimulation for interleukin/cytokine production, and kill hapten-modified or tumor cells in model systems both in vitro and in vivo. T cells expressing chimeric receptors made of antitumor antibodies are able to discriminate between a tumor and normal cell with negligible bystander cytotoxicity. Further studies should be carried out to evaluate and optimize the persistence, homing patterns and reactivation potential of T-bodies in the body.
Eshhar
Z
Z
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. lieshhar@weizmann.weizmann.ac.il
D000912:Antibodies, Neoplasm / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry* / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000922:Immunotoxins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry* / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology* / Q000627:therapeutic use; D014301:Trinitrobenzenes / Q000276:immunology
D000912:Antibodies, Neoplasm; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D011948:Receptors, Antigen, T-Cell; D014301:Trinitrobenzenes