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Biomacromolecules ; 21(2): 621-629, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31800235

RESUMO

Although current vaccine technology induces sufficient antibody responses to prophylactically ward off viral infections, an anticancer vaccine that directs the patient's immune system to directly fight extant malignant cells will require inducing Th1 and cytotoxic T lymphocyte responses in addition to antibody-mediated activities. Thus, new mechanisms are necessary to deliver antigen to cells in the lymphatic system that will induce these responses. To this end, we have developed a cholesterol-bearing pullulan (CHP) self-assembly nanogel of less than 100 nm, which we have now further modified to be anionic by carboxyl group substitution. Overall, the nanogel-protected antigens during transport to the lymphatic system and converting the vehicle to an anionic charge improved interactions with antigen-presenting cells. We further show that these modified nanogels are a more efficient system for delivering antigen to antigen-presenting cells, particularly langerin-expressing cells, and that this induced significant adaptive immunity. Therefore, we think that this technology could be used to improve anticancer immunotherapies.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Vacinas/administração & dosagem , Vacinas/química , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Sistemas de Liberação de Medicamentos , Epitopos , Feminino , Imunoglobulina G/sangue , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Nanogéis/química , Ovalbumina/administração & dosagem , Ovalbumina/farmacocinética , Polissacarídeos/química , Células RAW 264.7 , Vacinas/farmacologia
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