In vivo targeting of an anti-tumor antibody coupled to antigenic MHC class I complexes induces specific growth inhibition and regression of established syngeneic tumor grafts.
Data(s) |
2003
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Resumo |
The concept of antibody-mediated targeting of antigenic MHC/peptide complexes on tumor cells in order to sensitize them to T-lymphocyte cytotoxicity represents an attractive new immunotherapy strategy. In vitro experiments have shown that an antibody chemically conjugated or fused to monomeric MHC/peptide can be oligomerized on the surface of tumor cells, rendering them susceptible to efficient lysis by MHC-peptide restricted specific T-cell clones. However, this strategy has not yet been tested entirely in vivo in immunocompetent animals. To this aim, we took advantage of OT-1 mice which have a transgenic T-cell receptor specific for the ovalbumin (ova) immunodominant peptide (257-264) expressed in the context of the MHC class I H-2K(b). We prepared and characterized conjugates between the Fab' fragment from a high-affinity monoclonal antibody to carcinoembryonic antigen (CEA) and the H-2K(b) /ova peptide complex. First, we showed in OT-1 mice that the grafting and growth of a syngeneic colon carcinoma line transfected with CEA could be specifically inhibited by systemic injections of the conjugate. Next, using CEA transgenic C57BL/6 mice adoptively transferred with OT-1 spleen cells and immunized with ovalbumin, we demonstrated that systemic injections of the anti-CEA-H-2K(b) /ova conjugate could induce specific growth inhibition and regression of well-established, palpable subcutaneous grafts from the syngeneic CEA-transfected colon carcinoma line. These results, obtained in a well-characterized syngeneic carcinoma model, demonstrate that the antibody-MHC/peptide strategy can function in vivo. Further preclinical experimental studies, using an anti-viral T-cell response, will be performed before this new form of immunotherapy can be considered for clinical use. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_7767EE02583B isbn:1424-9634 pmid:12916958 |
Idioma(s) |
en |
Fonte |
Cancer Immunity, vol. 3, pp. 11 |
Palavras-Chave | #Animals; Antibodies, Monoclonal; Carcinoembryonic Antigen; Cell Division; Cytotoxicity, Immunologic; Female; H-2 Antigens; Humans; Immunoconjugates; Immunoglobulin Fab Fragments; Immunotherapy, Adoptive; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Mice, Transgenic; Neoplasm Transplantation; Neoplasms, Experimental; Ovalbumin; Remission Induction; Spleen; T-Lymphocytes, Cytotoxic; Transplantation, Isogeneic |
Tipo |
info:eu-repo/semantics/article article |