T-cell receptor-like antibodies: novel reagents for clinical cancer immunology and immunotherapy.
Major histocompatibility complex class I molecules play a central role in the immune response against a variety of cells that have undergone malignant transformation by shaping the T-cell repertoire and presenting peptide antigens from endogeneous antigens to CD8+ cytotoxic T-cells. Diseased tumor or virus-infected cells are present on class I major histocompatibility complex molecule peptides that are derived from tumor-associated antigens or viral-derived proteins. Due to their unique specificity, such major histocompatibility complex-peptide complexes are a desirable target for novel approaches in immunotherapy. Targeted delivery of toxins or other cytotoxic drugs to cells which express specific major histocompatibility complex-peptide complexes that are involved in the immune response against cancer or viral infections would allow for a specific immunotherapeutic treatment of these diseases. It has recently been demonstrated that antibodies with the antigen-specific, major histocompatibility complex-restricted specificity of T-cells can be generated by taking advantage of the selection power of phage display technology. In addition to their tumor targeting capabilities, antibodies that mimic the fine specificity of T-cell receptors can serve as valuable research reagents that enable study of human class I peptide-major histocompatibility complex ligand presentation, as well as T-cell receptor peptide-major histocompatibility complex interactions. T-cell receptor-like antibody molecules may prove to be useful tools for studying major histocompatibility complex class I antigen presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases and autoimmune disorders.
Noy
Roy
R
Technion-Israel Institute of Technology, Faculty of Biology, Haifa 32000, Israel.
Eppel
Malka
M
Haus-Cohen
Maya
M
Klechevsky
Einav
E
Mekler
Orian
O
Michaeli
Yaeil
Y
Denkberg
Galit
G
Reiter
Yoram
Y
D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D000917:Antibody Formation; D017951:Antigen Presentation; D000951:Antigens, Neoplasm; D000939:Epitopes; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D000922:Immunotoxins; D008024:Ligands; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D000906:Antibodies; D000951:Antigens, Neoplasm; D000939:Epitopes; D000922:Immunotoxins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell