Article: article from journal or magazin.
Redirecting anti-viral CTL against cancer cells by surface targeting of monomeric MHC class I-viral peptide conjugated to antibody fragments.
To combine the advantage of both the tumor targeting capacity of high affinity monoclonal antibodies (mAbs) and the potent killing properties of cytotoxic T lymphocytes (CTL), we investigated the activity of conjugates made by coupling single Fab' fragments, from mAbs specific for tumor cell surface antigens, to monomeric HLA-A2 complexes containing the immunodominant influenza-matrix peptide 58-66. In solution, the monovalent 95 kDa Fab-HLA-A2/Flu conjugates did not activate influenza-specific CTL. However, when targeted to tumor cells expressing the relevant tumor-associated antigen, the conjugates induced CTL activation and efficient tumor cell lysis, as a result of MHC/peptide surface oligomerization. The highly specific and sensitive in vitro cytotoxicity results presented suggest that injection of Fab-MHC/peptide conjugates could represent a new form of immunotherapy, bridging antibody and T lymphocyte attack on cancer cells.
Antibodies, Monoclonal/immunology, Antibodies, Monoclonal/pharmacology, Calcium/metabolism, Coculture Techniques, Cytotoxicity, Immunologic/drug effects, Flow Cytometry/methods, HLA-A2 Antigen/genetics, HLA-A2 Antigen/immunology, Humans, Immunoconjugates/immunology, Immunoglobulin Fragments/immunology, Inhibitory Concentration 50, Neoplasms/immunology, Neoplasms/pathology, Peptide Fragments/immunology, Recombinant Proteins/immunology, T-Lymphocytes, Cytotoxic/cytology, T-Lymphocytes, Cytotoxic/immunology, Tumor Cells, Cultured/drug effects, Tumor Cells, Cultured/immunology, Viral Matrix Proteins/immunology
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