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Spatiotemporal coordination of antigen presentation and co-stimulatory signal for enhanced anti-tumor vaccination.
Peng, Sha; Yan, Yumeng; Ogino, Kenji; Ma, Guanghui; Xia, Yufei.
Afiliación
  • Peng S; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan; Inst
  • Yan Y; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
  • Ogino K; Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan; Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan.
  • Ma G; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan; Univ
  • Xia Y; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address: yfxia@ipe.ac.cn.
J Control Release ; 374: 312-324, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39153722
ABSTRACT
Controlled-release systems enhance anti-tumor effects by leveraging local antigen persistence for antigen-presenting cells (APCs) recruitment and T cell engagement. However, constant antigen presentation alone tends to induce dysfunction in tumor-specific CD8+ T cells, neglecting the synergistic effects of co-stimulatory signal. To address this, we developed a soft particle-stabilized emulsion (SPE) to deliver lipopeptides with controlled release profiles by adjusting their hydrophobic chain lengths C6-SPE (fast release), C10-SPE (medium release), and C16-SPE (slow release). Following administration, C6-SPE release antigen rapidly, inducing early antigen presentation, whereas C16-SPE's slow-release delays antigen presentation. Both scenarios missed the critical window for coordinating with the expression of CD86, leading to either T cell apoptosis or suboptimal activation. In contrast, C10-SPE achieved a spatiotemporally synergetic effect of the MHC-I-peptide complex and co-stimulatory signal (CD86), leading to effective dendritic cell (DC) activation, enhanced T cell activation, and tumor regression in EG7-OVA bearing mice. Additionally, co-delivery of cytosine-phosphate-guanine (CpG) with SPE provided a sustained expression of the CD86 window for DC activation, improving the immune response and producing robust anti-tumor effects with C6-SPE comparable to C10-SPE. These findings highlight that synchronizing the spatiotemporal dynamics of antigen presentation and APC activation may confer an optimal strategy for enhanced vaccinations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Presentación de Antígeno / Vacunas contra el Cáncer / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Presentación de Antígeno / Vacunas contra el Cáncer / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos