PMID- 37891435
OWN - NLM
STAT- MEDLINE
DCOM- 20231130
LR  - 20240320
IS  - 1474-1784 (Electronic)
IS  - 1474-1776 (Print)
IS  - 1474-1776 (Linking)
VI  - 22
IP  - 12
DP  - 2023 Dec
TI  - T cell receptor therapeutics: immunological targeting of the intracellular cancer 
      proteome.
PG  - 996-1017
LID - 10.1038/s41573-023-00809-z [doi]
AB  - The T cell receptor (TCR) complex is a naturally occurring antigen sensor that 
      detects, amplifies and coordinates cellular immune responses to epitopes derived 
      from cell surface and intracellular proteins. Thus, TCRs enable the targeting of 
      proteins selectively expressed by cancer cells, including neoantigens, cancer 
      germline antigens and viral oncoproteins. As such, TCRs have provided the basis 
      for an emerging class of oncology therapeutics. Herein, we review the current 
      cancer treatment landscape using TCRs and TCR-like molecules. This includes 
      adoptive cell transfer of T cells expressing endogenous or engineered TCRs, TCR 
      bispecific engagers and antibodies specific for human leukocyte antigen 
      (HLA)-bound peptides (TCR mimics). We discuss the unique complexities associated 
      with the clinical development of these therapeutics, such as HLA restriction, TCR 
      retrieval, potency assessment and the potential for cross-reactivity. In 
      addition, we highlight emerging clinical data that establish the antitumour 
      potential of TCR-based therapies, including tumour-infiltrating lymphocytes, for 
      the treatment of diverse human malignancies. Finally, we explore the future of 
      TCR therapeutics, including emerging genome editing methods to safely enhance 
      potency and strategies to streamline patient identification.
CI  - (c) 2023. Springer Nature Limited.
FAU - Klebanoff, Christopher A
AU  - Klebanoff CA
AUID- ORCID: 0000-0001-9645-3896
AD  - Memorial Sloan Kettering Cancer Center (MSKCC), Human Oncology and Pathogenesis 
      Program, New York, NY, USA. klebanoc@mskcc.org.
FAU - Chandran, Smita S
AU  - Chandran SS
AD  - Memorial Sloan Kettering Cancer Center (MSKCC), Human Oncology and Pathogenesis 
      Program, New York, NY, USA.
AD  - Parker Institute for Cancer Immunotherapy, New York, NY, USA.
AD  - Weill Cornell Medical College, Cornell University, New York, NY, USA.
FAU - Baker, Brian M
AU  - Baker BM
AUID- ORCID: 0000-0002-0864-0964
AD  - Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, 
      ID, USA.
AD  - The Harper Cancer Research Institute, University of Notre Dame, Notre Dame, ID, 
      USA.
FAU - Quezada, Sergio A
AU  - Quezada SA
AD  - Cancer Immunology Unit, Research Department of Haematology, University College 
      London Cancer Institute, London, UK.
AD  - Cancer Research UK Lung Cancer Centre of Excellence, University College London 
      Cancer Institute, London, UK.
AD  - Achilles Therapeutics, London, UK.
FAU - Ribas, Antoni
AU  - Ribas A
AUID- ORCID: 0000-0003-3669-8458
AD  - Jonsson Comprehensive Cancer Center at the University of California, Los Angeles 
      (UCLA), Los Angeles, CA, USA.
LA  - eng
GR  - R01 CA269733/CA/NCI NIH HHS/United States
GR  - R01 CA286507/CA/NCI NIH HHS/United States
GR  - R35 CA197633/CA/NCI NIH HHS/United States
GR  - P50 CA217694/CA/NCI NIH HHS/United States
GR  - R35 GM118166/GM/NIGMS NIH HHS/United States
GR  - P01 CA168585/CA/NCI NIH HHS/United States
GR  - R37 CA259177/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20231027
PL  - England
TA  - Nat Rev Drug Discov
JT  - Nature reviews. Drug discovery
JID - 101124171
RN  - 0 (Proteome)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Humans
MH  - *Proteome/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Antigens, Neoplasm
MH  - Receptors, Antigen, T-Cell
MH  - *Neoplasms/drug therapy
PMC - PMC10947610
MID - NIHMS1967991
COIS- Competing interests: C.A.K. and S.S.C. are inventors on patents related to TCR 
      discovery and public neoantigen-specific TCRs and are recipients of licensing 
      revenue shared according to MSKCC institutional policies. C.A.K. has consulted 
      for or is on the scientific advisory boards for Achilles Therapeutics, Affini-T 
      Therapeutics, Aleta BioTherapeutics, Bellicum Pharmaceuticals, Bristol Myers 
      Squibb, Catamaran Bio, Cell Design Labs, Decheng Capital, G1 Therapeutics, Klus 
      Pharma, Obsidian Therapeutics, PACT Pharma, Roche/Genentech and T-knife. C.A.K. 
      is a scientific co-founder and equity holder in Affini-T Therapeutics. B.M.B. is 
      an inventor on patents related to TCR engineering and neoantigen discovery, has 
      consulted for Eureka Therapeutics and EnaraBio, and is on the scientific advisory 
      board of T-cure Bioscience. S.A.Q is an inventor in patents related to the use of 
      T cell therapies targeting tumour clonal neoantigens in cancer. S.A.Q. is also a 
      founder, CSO, and equity holder of Achilles Therapeutics. A.R. reports personal 
      fees from Amgen, Chugai, Genentech, Merck, Novartis, Roche, Sanofi, Vedanta, 4C 
      Biomed, Appia, Apricity, Arcus, Highlight, Compugen, ImaginAb, Kalthera/ImmPACT 
      Bio, MapKure, Merus, Rgenix, Lutris, Nextech, PACT Pharma, Synthekine, Tango, 
      Advaxis, CytomX, Five Prime, RAPT, Isoplexis, and Kite/Gilead and has received 
      grants from Agilent and Bristol Myers Squibb outside the submitted work.
EDAT- 2023/10/28 11:42
MHDA- 2023/11/30 06:43
PMCR- 2024/06/01
CRDT- 2023/10/27 23:39
PHST- 2023/09/08 00:00 [accepted]
PHST- 2024/06/01 00:00 [pmc-release]
PHST- 2023/11/30 06:43 [medline]
PHST- 2023/10/28 11:42 [pubmed]
PHST- 2023/10/27 23:39 [entrez]
AID - 10.1038/s41573-023-00809-z [pii]
AID - 10.1038/s41573-023-00809-z [doi]
PST - ppublish
SO  - Nat Rev Drug Discov. 2023 Dec;22(12):996-1017. doi: 10.1038/s41573-023-00809-z. 
      Epub 2023 Oct 27.