Programming CAR T cell tumor recognition: Tuned antigen sensing and logic gating Review

   


Authors: Hamieh, M.; Mansilla-Soto, J.; Rivière, I.; Sadelain, M.
Review Title: Programming CAR T cell tumor recognition: Tuned antigen sensing and logic gating
Abstract: The success of chimeric antigen receptor (CAR) T cells targeting B-cell malignancies propelled the field of synthetic immunology and raised hopes to treat solid tumors in a similar fashion. Antigen escape and the paucity of tumor-restricted CAR targets are recognized challenges to fulfilling this prospect. Recent advances in CAR T cell engineering extend the toolbox of chimeric receptors available to calibrate antigen sensitivity and combine receptors to create adapted tumor-sensing T cells. Emerging engineering strategies to lower the threshold for effective antigen recognition, when needed, and enable composite antigen recognition hold great promise for overcoming tumor heterogeneity and curbing off-tumor toxicities. SIGNIFICANCE: Improving the clinical efficacy of CAR T cell therapies will require engineering T cells that overcome heterogeneous and low-abundance target expression while minimizing reactivity to normal tissues. Recent advances in CAR design and logic gating are poised to extend the success of CAR T cell therapies beyond B-cell malignancies. ©2023 The Authors; Published by the American Association for Cancer Research.
Keywords: treatment outcome; genetics; neoplasm; neoplasms; t lymphocyte; t-lymphocytes; tumor antigen; antigens, neoplasm; receptors, antigen, t-cell; adoptive immunotherapy; immunotherapy, adoptive; lymphocyte antigen receptor; procedures; humans; human
Journal Title: Cancer Discovery
Volume: 13
Issue: 4
ISSN: 2159-8274
Publisher: American Association for Cancer Research  
Date Published: 2023-04-01
Start Page: 829
End Page: 843
Language: English
DOI: 10.1158/2159-8290.Cd-23-0101
PUBMED: 36961206
PROVIDER: scopus
PMCID: PMC10068450
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85151575076&doi=10.1158%2f2159-8290.CD-23-0101&partnerID=40&md5=26d023e511ca6022918ff2bc907d654b
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding author is MSK author Michel Sadelain -- Export Date: 1 May 2023 -- Source: Scopus
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MSK Authors
  1. Jorge Mansilla-Soto
    49 Mansilla-Soto
  2. Michel W J Sadelain
    584 Sadelain
  3. Isabelle C Riviere
    241 Riviere
  4. Mohamad Hamieh
    27 Hamieh
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