1. Academic Validation
  2. Chimeric Exosomes Functionalized with STING Activation for Personalized Glioblastoma Immunotherapy

Chimeric Exosomes Functionalized with STING Activation for Personalized Glioblastoma Immunotherapy

  • Adv Sci (Weinh). 2023 Dec 10:e2306336. doi: 10.1002/advs.202306336.
Peng Bao 1 Hui-Yun Gu 2 Jing-Jie Ye 1 Jin-Lian He 1 Zhenlin Zhong 1 Ai-Xi Yu 2 Xian-Zheng Zhang 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
  • 2 Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, P. R. China.
Abstract

A critical challenge of existing Cancer vaccines is to orchestrate the demands of antigen-enriched furnishment and optimal antigen-presentation functionality within antigen-presenting cells (APCs). Here, a complementary immunotherapeutic strategy is developed using dendritic cell (DC)-tumor hybrid cell-derived chimeric exosomes loaded with stimulator of interferon genes (STING) agonists (DT-Exo-STING) for maximized tumor-specific T-cell immunity. These chimeric carriers are furnished with broad-spectrum antigen complexes to elicit a robust T-cell-mediated inflammatory program through direct self-presentation and indirect DC-to-T immunostimulatory pathway. This chimeric exosome-assisted delivery strategy possesses the merits versus off-the-shelf cyclic dinucleotide (CDN) delivery techniques in both the brilliant tissue-homing capacity, even across the intractable blood-brain barrier (BBB), and the desired cytosolic entry for enhanced STING-activating signaling. The improved antigen-presentation performance with this nanovaccine-driven STING activation further enhances tumor-specific T-cell immunoresponse. Thus, DT-Exo-STING reverses immunosuppressive glioblastoma microenvironments to pro-inflammatory, tumoricidal states, leading to an almost obliteration of intracranial primary lesions. Significantly, an upscaling option that harnesses autologous tumor tissues for personalized DT-Exo-STING vaccines increases sensitivity to immune checkpoint blockade (ICB) therapy and exerts systemic immune memory against post-operative glioma recrudesce. These findings represent an emerging method for glioblastoma immunotherapy, warranting further exploratory development in the clinical realm.

Keywords

STING activation; T cell responses; chimeric exosomes; glioblastoma; personalized immunotherapy.

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