T-Cell Receptor-Like Antibodies: Targeting the Intracellular Proteome Therapeutic Potential and Clinical Applications

• Main Authors: Maya Cohen, Yoram Reiter
• Format: Article
• Language: English
• Published: MDPI AG 2013-09-01
• Series: Antibodies
• Subjects: antibodies; antibody engineering; immunotoxins; MHC-peptide complex; phage display; recombinant antibodies; T-cell receptor; cancer immunotherapy
• Online Access: http://www.mdpi.com/2073-4468/2/3/517

Major histocompatibility complex (MHC) class I molecules are key in the immune response against malignant cells by shaping the T-cell repertoire and presenting peptides from endogenous antigens to CD8+ cytotoxic T cells. Because of their unique specificity, MHC-peptide complexes are a desirable target for novel immunotherapeutic approaches. These complexes can be targeted by recombinant T-cell receptors (TCRs). However, most TCRs produced thus far have affinities which are too low for target detection under normal assay conditions, and limited stability (due to their generation in a single-chain version). Developing high-affinity soluble antibody molecules endowed with a TCR-like specificity toward tumor epitopes, termed TCR-like antibodies, addresses the low affinity of TCRs. These TCR-like antibodies are being developed as a new immunotherapeutic class for targeting tumor cells and mediating their specific killing. In addition, these antibodies are valuable research reagents enabling the study of human class I peptide-MHC ligand-presentation and TCR–peptide–MHC interactions.