Improved induction of anti-melanoma T cells by adenovirus-5/3 fiber modification to target human DCs

Dafni Chondronasiou, Tracy Jane T.H.D. Eisden, Anita G.M. Stam, Qiana L. Matthews, Mert Icyuz, Erik Hooijberg, Igor Dmitriev, David T. Curiel, Tanja D. de Gruijl, Rieneke van de Ven

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8+ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. “Off-the-shelf” DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches.

Original languageEnglish
Article number42
JournalVaccines
Volume6
Issue number3
DOIs
StatePublished - Sep 2018

Keywords

  • Adenovirus (Ad)5/3
  • Dendritic cell targeting
  • MART-1
  • Melanoma
  • Melanoma-specific T cells
  • Sentinel lymph node

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    Chondronasiou, D., Eisden, T. J. T. H. D., Stam, A. G. M., Matthews, Q. L., Icyuz, M., Hooijberg, E., Dmitriev, I., Curiel, D. T., de Gruijl, T. D., & van de Ven, R. (2018). Improved induction of anti-melanoma T cells by adenovirus-5/3 fiber modification to target human DCs. Vaccines, 6(3), [42]. https://doi.org/10.3390/vaccines6030042