Retargeting CD19 Chimeric Antigen Receptor T Cells via Engineered CD19-Fusion Proteins.
Antigens, CD19
/ genetics
Antigens, Neoplasm
/ immunology
Cell Line, Tumor
HEK293 Cells
Humans
Immunotherapy, Adoptive
/ methods
Mutagenesis
Neoplasms
/ immunology
Protein Domains
/ genetics
Protein Engineering
Receptor, ErbB-2
/ antagonists & inhibitors
Receptors, Chimeric Antigen
/ immunology
Recombinant Fusion Proteins
/ genetics
Single-Chain Antibodies
/ genetics
T-Lymphocytes
/ immunology
CD19
chimeric antigen receptors
deep mutational scanning
protein fusion
protein solubility
yeast surface display
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
05 08 2019
05 08 2019
Historique:
pubmed:
27
6
2019
medline:
26
6
2020
entrez:
27
6
2019
Statut:
ppublish
Résumé
CD19-targeted chimeric antigen receptor (CAR) T-cells (CAR19s) show remarkable efficacy in the treatment of relapsed/refractory acute lymphocytic leukemia and Non-Hodgkin's lymphoma. However, the use of CAR T-cell therapy against CD19-negative hematological cancers and solid tumors has been challenging. We propose CD19-fusion proteins (CD19-FPs) to leverage the benefits of CAR19s while retargeting this validated cellular therapy to alternative tumor antigens. We demonstrate the ability of a fusion of CD19 extracellular domain (ECD) and a human epidermal growth factor receptor 2 (HER2) single-chain antibody fragment to retarget CAR19s to kill HER2
Identifiants
pubmed: 31242389
doi: 10.1021/acs.molpharmaceut.9b00418
doi:
Substances chimiques
Antigens, CD19
0
Antigens, Neoplasm
0
CD19 molecule, human
0
Receptors, Chimeric Antigen
0
Recombinant Fusion Proteins
0
Single-Chain Antibodies
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM