Linked Life Data

12916958

Source:http://linkedlifedata.com/resource/pubmed/id/12916958

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-8-14
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1424-9634
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12916958-Animals, pubmed-meshheading:12916958-Antibodies, Monoclonal, pubmed-meshheading:12916958-Carcinoembryonic Antigen, pubmed-meshheading:12916958-Cell Division, pubmed-meshheading:12916958-Cytotoxicity, Immunologic, pubmed-meshheading:12916958-Female, pubmed-meshheading:12916958-H-2 Antigens, pubmed-meshheading:12916958-Humans, pubmed-meshheading:12916958-Immunoconjugates, pubmed-meshheading:12916958-Immunoglobulin Fab Fragments, pubmed-meshheading:12916958-Immunotherapy, Adoptive, pubmed-meshheading:12916958-Male, pubmed-meshheading:12916958-Mice, pubmed-meshheading:12916958-Mice, Inbred C57BL, pubmed-meshheading:12916958-Mice, Nude, pubmed-meshheading:12916958-Mice, Transgenic, pubmed-meshheading:12916958-Neoplasm Transplantation, pubmed-meshheading:12916958-Neoplasms, Experimental, pubmed-meshheading:12916958-Ovalbumin, pubmed-meshheading:12916958-Remission Induction, pubmed-meshheading:12916958-Spleen, pubmed-meshheading:12916958-T-Lymphocytes, Cytotoxic, pubmed-meshheading:12916958-Transplantation, Isogeneic
pubmed:year
2003
pubmed:articleTitle
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.
pubmed:affiliation
Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't