Opportunities and challenges for TCR mimic antibodies in cancer therapy Journal Article

Authors: Chang, A. Y.; Gejman, R. S.; Brea, E. J.; Oh, C. Y.; Mathias, M. D.; Pankov, D.; Casey, E.; Dao, T.; Scheinberg, D. A.
Article Title: Opportunities and challenges for TCR mimic antibodies in cancer therapy
Abstract: ABSTRACT: Introduction: Monoclonal antibodies (mAbs) are potent cancer therapeutic agents, but exclusively recognize cell-surface targets whereas most cancer-associated proteins are found intracellularly. Hence, potential cancer therapy targets such as over expressed self-proteins, activated oncogenes, mutated tumor suppressors, and translocated gene products are not accessible to traditional mAb therapy. An emerging approach to target these epitopes is the use of TCR mimic mAbs (TCRm) that recognize epitopes similar to those of T cell receptors (TCR). Areas covered: TCRm antigens are composed of a linear peptide sequence derived from degraded proteins and presented in the context of cell-surface MHC molecules. We discuss how the nature of the TCRm epitopes provides both advantages (absolute tumor specificity and access to a new universe of important targets) and disadvantages (low density, MHC restriction, MHC down-regulation, and cross-reactive linear epitopes) to conventional mAb therapy. We will also discuss potential solutions to these obstacles. Expertopinion: TCRm combine the specificity of TCR recognition with the potency, pharmacologic properties, and versatility of mAbs. The structure and presentation of a TCRm epitope has important consequences related to the choice of targets, mAb design, available peptides and MHC subtype restrictions, possible cross-reactivity, and therapeutic activity. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Keywords: monoclonal antibody; oncogene; phage display; oncofetal antigen; tcr; cancer-testis antigen; tcr mimic; neoantigen
Journal Title: Expert Opinion on Biological Therapy
Volume: 16
Issue: 8
ISSN: 1471-2598
Publisher: Taylor & Francis Group  
Date Published: 2016-01-01
Start Page: 979
End Page: 987
Language: English
DOI: 10.1080/14712598.2016.1176138
PROVIDER: scopus
PMCID: PMC4936943
PUBMED: 27094818
Notes: Review -- Export Date: 2 August 2016 -- Source: Scopus
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MSK Authors
  1. Tao Dao
    57 Dao
  2. Dmitry D. Pankov
    18 Pankov
  3. Emily Catherine Casey
    9 Casey
  4. Melissa Divya Mathias
    14 Mathias
  5. Ron Shlomo Gejman
    8 Gejman
  6. Elliott Joseph Brea
    13 Brea
  7. Aaron   Chang
    10 Chang
  8. Claire   Oh
    4 Oh