Back to Search
Start Over
CAR-J cells for antibody discovery and lead optimization of TCR-like immunoglobulins
- Source :
- mAbs, article-version (VoR) Version of Record
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- 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.
- Subjects :
- major histocompatibility complex (MHC)
Immunology
Epitopes, T-Lymphocyte
Human leukocyte antigen
Jurkat cells
Immunotherapy, Adoptive
03 medical and health sciences
Jurkat Cells
0302 clinical medicine
Antigen
In vivo
Antigens, Neoplasm
Report
Antibodies, Bispecific
Immunology and Allergy
Humans
Receptor
chimeric antigen receptor (CAR)
030304 developmental biology
Immunoassay
0303 health sciences
Receptors, Chimeric Antigen
biology
Chemistry
T-cell receptor
T-cell receptor (TCR)
cellular assay
Lead identification
Chimeric antigen receptor
Cell biology
TCR-like antibodies (TCRL)
human leukocyte antigen (HLA)
T-cell bispecific antibodies (TCB)
030220 oncology & carcinogenesis
biology.protein
Wilms tumor protein (WT1)
Antibody
Subjects
Details
- Language :
- English
- ISSN :
- 19420870 and 19420862
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- mAbs
- Accession number :
- edsair.doi.dedup.....12b8dd7e8bafef97b7b999e60412af7b