Redirecting anti-viral CTL against cancer cells by surface targeting of monomeric MHC class I-viral peptide conjugated to antibody fragments.

Abstract

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.

• Authors: B Robert, P Guillaume, I Luescher, M A Doucey, J C Cerottini, P Romero, J P Mach
• Journal: Cancer immunity (Cancer Immun) Vol. 1 Pg. 2 (Mar 30 2001) ISSN: 1424-9634 [Electronic] United States
• PMID: 12747763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• HLA-A2 Antigen
• Immunoconjugates
• Immunoglobulin Fragments
• Peptide Fragments
• Recombinant Proteins
• Viral Matrix Proteins
• influenza matrix peptide (58-66)
• Calcium

Topics

• Antibodies, Monoclonal (immunology, pharmacology)
• Calcium (metabolism)
• Coculture Techniques
• Cytotoxicity, Immunologic (drug effects)
• Flow Cytometry (methods)
• HLA-A2 Antigen (genetics, immunology)
• Humans
• Immunoconjugates (immunology)
• Immunoglobulin Fragments (immunology)
• Inhibitory Concentration 50
• Neoplasms (immunology, pathology)
• Peptide Fragments (immunology)
• Recombinant Proteins (immunology)
• T-Lymphocytes, Cytotoxic (cytology, immunology, metabolism)
• Tumor Cells, Cultured (drug effects, immunology)
• Viral Matrix Proteins (immunology)