Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment.
Nano Lett
; 22(17): 6866-6876, 2022 09 14.
Article
em En
| MEDLINE
| ID: mdl-35926215
ABSTRACT
Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3ß1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4ß1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microambiente Tumoral
/
Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos