Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains.
Nat Commun
; 11(1): 283, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31941907
Chimeric antigen receptor (CAR)-expressing T cells targeting B-cell maturation antigen (BCMA) have activity against multiple myeloma, but improvements in anti-BCMA CARs are needed. We demonstrated recipient anti-CAR T-cell responses against a murine single-chain variable fragment (scFv) used clinically in anti-BCMA CARs. To bypass potential anti-CAR immunogenicity and to reduce CAR binding domain size, here we designed CARs with antigen-recognition domains consisting of only a fully human heavy-chain variable domain without a light-chain domain. A CAR designated FHVH33-CD8BBZ contains a fully human heavy-chain variable domain (FHVH) plus 4-1BB and CD3ζ domains. T cells expressing FHVH33-CD8BBZ exhibit similar cytokine release, degranulation, and mouse tumor eradication as a CAR that is identical except for substitution of a scFv for FHVH33. Inclusion of 4-1BB is critical for reducing activation-induced cell death and promoting survival of T cells expressing FHVH33-containing CARs. Our results indicate that heavy-chain-only anti-BCMA CARs are suitable for evaluation in a clinical trial.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Cadeias Pesadas de Imunoglobulinas
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Receptores de Antígenos Quiméricos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos