A novel bispecific nanobody with PD-L1/TIGIT dual immune checkpoint blockade.
Biochem Biophys Res Commun
; 531(2): 144-151, 2020 10 15.
Article
en En
| MEDLINE
| ID: mdl-32782142
ABSTRACT
Cancer immunotherapy have changed the paradigm of cancer treatment, but there remains a great need for improvement given that less patients with tumors respond to the treatment of PD-1/PD-L1 blockade. TIGIT (also called T cell immunoreceptor with Ig and ITIM domains), a novel immune checkpoint molecule, has been shown a promising target for drug development of immunotherapy. Here we report generation and characterization of a multivalent bispecific antibody (BsAb) that co-targets PD-L1 and TIGIT. The BsAb consists of tetravalent anti-PD-L1 Fc-fusion nanobody (Nb) and tetravalent anti-TIGIT Nb. The parental anti-PD-L1 Nb showed high specificity and affinity to primate PD-L1, the enhanced T cell activity in vitro and anti-tumor activity in vivo. Similarly, the parental anti-TIGIT Nb showed the high specificity and affinity to primate TIGIT and the enhanced T cell activity. Furthermore, we demonstrated that the BsAb retained high blocking activity towards PD-1/PD-L1 or TIGIT/CD155 interaction. The BsAb synergistically enhanced T cell activities in vitro compared to two parental Nbs. Taken together, we obtained a multivalent BsAb blocking biological function of PD-L1 and TIGIT and it is worthy to further study the anti-tumor activities of this BsAb in vivo.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores Inmunológicos
/
Anticuerpos Biespecíficos
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Antígeno B7-H1
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Anticuerpos de Dominio Único
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Inhibidores de Puntos de Control Inmunológico
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Article
País de afiliación:
China