title: TCR-MHC/peptide interaction: prospects for new anti-tumoral agents.
abstract: Tumor-related antigens can be presented as peptides forming complexes with major histocompatibility complex (MHC) molecules that interact with T-cell receptors, thus generating an immunologic anti-tumor response. Unfortunately, however, this response can be decreased by many effectors and pathways. On the other hand, such peptide-MHC complexes are unique starting points for therapeutic intervention. We present strategies for eliciting an anti-tumoral response by T-cell receptor-based fusion proteins with interleukin (IL)2 and antibody constant region domains, superantigens, and T-cell recruiting antibodies, as well as using genetically modified autologous T-cells as effectors. Another strategy is to direct peptide-MHC complexes to tumors as fusion proteins with an antibody-derived targeting moiety. Finally, we describe T-cell receptor-mimicking antibodies and antibody conjugates as anti tumoral agents.
authors.affiliation: Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Weidle
authors.affiliation: Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Guy
authors.initials: G
authors.lastname: Georges
authors.affiliation: Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Tiefenthaler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006649:Histocompatibility Antigens / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006649:Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Antibody-MHC fusion proteins; T-cell receptor; T-cell receptor-based fusion proteins; chimeric antigen receptors; immunological synapse; review