Peptide-scFv antigen recognition domains effectively confer CAR T cell multiantigen specificity.
Cell Rep Med
; 5(2): 101422, 2024 Feb 20.
Article
em En
| MEDLINE
| ID: mdl-38350450
ABSTRACT
The emergence of immune escape is a significant roadblock to developing effective chimeric antigen receptor (CAR) T cell therapies against hematological malignancies, including acute myeloid leukemia (AML). Here, we demonstrate feasibility of targeting two antigens simultaneously by combining a GRP78-specific peptide antigen recognition domain with a CD123-specific scFv to generate a peptide-scFv bispecific antigen recognition domain (78.123). To achieve this, we test linkers with varying length and flexibility and perform immunophenotypic and functional characterization. We demonstrate that bispecific CAR T cells successfully recognize and kill tumor cells that express GRP78, CD123, or both antigens and have improved antitumor activity compared to their monospecific counterparts when both antigens are expressed. Protein structure prediction suggests that linker length and compactness influence the functionality of the generated bispecific CARs. Thus, we present a bispecific CAR design strategy to prevent immune escape in AML that can be extended to other peptide-scFv combinations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
/
Receptores de Antígenos Quiméricos
Limite:
Humans
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos