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Article summary:
1. Monoclonal antibodies (mAbs) are effective therapeutic agents for cancer immunotherapy due to their high affinity and target specificity.
2. TCR-mimic (TCRm) Abs, which are mAbs specific for peptide tumor antigens presented by major histocompatability complex (MHC) proteins, are an emerging immunotherapy modality capable of recognizing a broad array of tumor antigens expressed at low levels on the tumor cell surface.
3. A new approach for the isolation of TCRm Abs focuses on Abs known to engage the pMHC in a ‘conventional’ TCR-like manner, with the criterion being binding to the pMHC similar to the known, canonical diagonal ‘footprints’ seen in the majority of alpha-beta TCR complexes with MHC.
Article analysis:
This article is generally reliable and trustworthy as it provides a comprehensive overview of monoclonal antibodies (mAbs) as an effective therapeutic agent for cancer immunotherapy and introduces a new approach for isolating peptide–MHC-restricted antibodies (TCRm Abs). The article is well-structured and clearly explains how TCRm Abs can be used in different formats to achieve different modalities of target killing, such as IgG for antibody–drug conjugates (ADC) and/or antibody-dependent cellular cytotoxicity (ADCC), bispecific T cell engager (BiTEs), and in the context of chimeric antigen receptor-T (CAR-T). It also provides detailed information about how conventional approaches such as mouse hybridoma and phage-display library technologies have been used to isolate TCRm Abs but have had low hit rates due to Ab binding sites not being evolved for antigen-specific recognition of the composite peptide–major histocompatibility complex (pMHC) surface.
The article is unbiased and does not contain any promotional content or partiality towards any particular method or technology. It presents both sides equally by providing detailed information about conventional approaches as well as introducing a new approach that focuses on Abs known to engage pMHC in a ‘conventional’ TCR-like manner. The article also mentions potential risks associated with off-target MHC reactivity if TCRm docking modes are off-kilter and exhibit a preponderance of MHC helical contacts.
The only potential issue with this article is that it does not provide any evidence or data to support its claims about conventional approaches having low hit rates or its proposed new approach being more successful in isolating peptide–MHC restricted antibodies. However, this could be due to space constraints rather than intentional omission.