Nanobody Based Dual Specific CARs.
Int J Mol Sci
; 19(2)2018 Jan 30.
Article
en En
| MEDLINE
| ID: mdl-29385713
ABSTRACT
Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes de Fusión
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Receptores de Antígenos de Linfocitos T
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Linfocitos T
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Anticuerpos de Dominio Único
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
Bélgica