Article
Promoting antigen escape from dendritic cell endosomes potentiates anti-tumoral immunity

https://doi.org/10.1016/j.xcrm.2022.100534Get rights and content
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Highlights

  • Accum-linked antigen enhances antigen processing and presentation

  • Pulsed dendritic cells elicit potent effector T cell responses

  • Therapeutic vaccination using allogeneic DCs controls pre-established tumors

  • The vaccine boosts tumor-infiltrating lymphocytes and increases the CD8/Treg ratio

Summary

The cross-presenting capacity of dendritic cells (DCs) can be limited by non-specific degradation during endosome maturation. To bypass this limitation, we present in this study a new Accum-based formulation designed to promote endosome-to-cytosol escape. Treatment of primary DCs with Accum linked to the xenoantigen ovalbumin (OVA) triggers endosomal damages and enhances protein processing. Despite multiple challenges using ascending doses of tumor cells, DC prophylactic vaccination results in complete protection due to increased levels of effector CD4 and CD8 T cells as well as high production of pro-inflammatory mediators. When combined with anti-PD-1, therapeutic vaccination using both syngeneic and allogeneic Accum-OVA-pulsed DCs triggers potent anti-tumoral responses. The net outcome culminates in increased CD11c, CD8, and NK infiltration along with a high CD8/Treg ratio. These highly favorable therapeutic effects highlight the promising potential of Accum as a distinct and potent technology platform suitable for the design of next generation cell cancer vaccines.

Keywords

dendritic cells
endosomes
Accum
antigen cross-presentation
anti-tumoral immunity
immune checkpoint inhibitors
tumor-infiltrating lymphocytes

Data and code availability

  • Original microscopy data reported in this paper will be shared by the lead contact upon request.

  • This paper does not report original code. Antigen 3D structure modeling and accessible amino acids identification were done using previously available RCSB PDB and Swiss-Model Expasy free access software.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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