Selective antibody-mediated targeting of class I MHC to EGFR-expressing tumor cells induces potent antitumor CTL activity in vitro and in vivo
| Autor: | Dina Segal, Winfried S. Wels, Kfir Oved, Yoram Reiter, Hila Novak, Roy Noy |
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| Rok vydání: | 2006 |
| Předmět: |
Cytotoxicity
Immunologic Cancer Research medicine.drug_class T cell Recombinant Fusion Proteins Biology Monoclonal antibody Major histocompatibility complex Mice Antigen In vivo Neoplasms medicine Cytotoxic T cell Animals Humans Mice Inbred BALB C Histocompatibility Antigens Class I Antibodies Monoclonal Fusion protein Virology Xenograft Model Antitumor Assays ErbB Receptors medicine.anatomical_structure Oncology biology.protein Cancer research Immunotherapy CD8 Single-Chain Antibodies T-Lymphocytes Cytotoxic |
| Zdroj: | International journal of cancer. 120(2) |
| ISSN: | 0020-7136 |
| Popis: | Epidermal growth factor receptor (EGFR) is highly overexpressed in many tumor types. We present a new fusion molecule that can target solid tumors that express EGFR. The fusion molecule combines the advantage(s) of the well-established tumor targeting capabilities of high affinity recombinant fragments of antibodies with the known efficient, specific and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC/peptide complexes. A recombinant chimeric molecule was created by the genetic fusion of the scFv antibody fragment derived from the anti-EGFR monoclonal antibody C225, to monomeric single-chain HLA-A2 complexes containing immunodominant tumor or viral-specific peptides. The fusion protein can induce very efficiently CTL-dependent lysis of EGFR-expressing tumor cells regardless of the expression of self peptide-MHC complexes. Moreover, the molecule exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results indicate that recombinant scFv-MHC-peptide fusion molecules might represent a novel and powerful approach to immunotherapy of solid tumors, bridging antibody and T lymphocyte attack on cancer cells. © 2006 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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