PMID- 33136521
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210920
IS  - 1942-0870 (Electronic)
IS  - 1942-0862 (Print)
IS  - 1942-0862 (Linking)
VI  - 12
IP  - 1
DP  - 2020 Jan-Dec
TI  - CAR-J cells for antibody discovery and lead optimization of TCR-like 
      immunoglobulins.
PG  - 1840709
LID - 10.1080/19420862.2020.1840709 [doi]
LID - 1840709
AB  - T-cell bispecific antibodies (TCBs) are a novel class of engineered 
      immunoglobulins that unite monovalent binding to the T-cell receptor (TCR) CD3e 
      chain and bivalent binding to tumor-associated antigens in order to recruit and 
      activate T-cells for tumor cell killing. In vivo, T-cell activation is usually 
      initiated via the interaction of the TCR with the peptide-HLA complex formed by 
      the human leukocyte antigen (HLA) and peptides derived from intracellular 
      proteins. TCR-like antibodies (TCRLs) that recognize pHLA-epitopes extend the 
      target space of TCBs to peptides derived from intracellular proteins, such as 
      those overexpressed during oncogenesis or created via mutations found in cancer. 
      One challenge during lead identification of TCRL-TCBs is to identify TCRLs that 
      specifically, and ideally exclusively, recognize the desired pHLA, but not 
      unrelated pHLAs. In order to identify TCRLs suitable for TCRL-TCBs, large numbers 
      of TCRLs have to be tested in the TCB format. Here, we propose a novel approach 
      using chimeric antigen receptors (CARs) to facilitate the identification of 
      highly selective TCRLs. In this new so-called TCRL-CAR-J approach, 
      TCRL-candidates are transduced as CARs into Jurkat reporter-cells, and 
      subsequently assessed for their specificity profile. This work demonstrates that 
      the CAR-J reporter-cell assay can be applied to predict the profile of TCRL-TCBs 
      without the need to produce each candidate in the final TCB format. It is 
      therefore useful in streamlining the identification of TCRL-TCBs.
FAU - Jost, Christian
AU  - Jost C
AUID- ORCID: 0000-0002-4169-5879
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
AD  - Athebio AG , Zurich, Switzerland.
FAU - Darowski, Diana
AU  - Darowski D
AUID- ORCID: 0000-0002-8778-7920
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Challier, John
AU  - Challier J
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Pulko, Vesna
AU  - Pulko V
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Hanisch, Lydia J
AU  - Hanisch LJ
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Xu, Wei
AU  - Xu W
AUID- ORCID: 0000-0001-5404-7523
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Mossner, Ekkehard
AU  - Mossner E
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Bujotzek, Alexander
AU  - Bujotzek A
AD  - Roche Innovation Center Munich, Roche Pharma Research & Early Development , 
      Penzberg, Germany.
FAU - Klostermann, Stefan
AU  - Klostermann S
AD  - Roche Innovation Center Munich, Roche Pharma Research & Early Development , 
      Penzberg, Germany.
FAU - Umana, Pablo
AU  - Umana P
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
FAU - Kontermann, Roland E
AU  - Kontermann RE
AUID- ORCID: 0000-0001-7139-1350
AD  - University of Stuttgart , Stuttgart, Germany.
FAU - Klein, Christian
AU  - Klein C
AUID- ORCID: 0000-0001-7594-7280
AD  - Roche Innovation Center Zurich, Roche Pharma Research & Early Development , 
      Schlieren, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - MAbs
JT  - mAbs
JID - 101479829
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Receptors, Chimeric Antigen)
SB  - IM
MH  - Antibodies, Bispecific/*analysis
MH  - Antigens, Neoplasm/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Humans
MH  - Immunoassay/*methods
MH  - Immunotherapy, Adoptive/*methods
MH  - Jurkat Cells
MH  - Receptors, Chimeric Antigen/immunology
PMC - PMC7646475
OTO - NOTNLM
OT  - Lead identification
OT  - T-cell bispecific antibodies (TCB)
OT  - T-cell receptor (TCR)
OT  - TCR-like antibodies (TCRL)
OT  - Wilms tumor protein (WT1)
OT  - cellular assay
OT  - chimeric antigen receptor (CAR)
OT  - human leukocyte antigen (HLA)
OT  - major histocompatibility complex (MHC)
EDAT- 2020/11/03 06:00
MHDA- 2021/09/21 06:00
PMCR- 2020/11/02
CRDT- 2020/11/02 17:11
PHST- 2020/11/02 17:11 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2020/11/02 00:00 [pmc-release]
AID - 1840709 [pii]
AID - 10.1080/19420862.2020.1840709 [doi]
PST - ppublish
SO  - MAbs. 2020 Jan-Dec;12(1):1840709. doi: 10.1080/19420862.2020.1840709.