Molecular Therapy: Methods & Clinical Development (Jun 2023)

Capsid-modified adeno-associated virus vectors as novel vaccine platform for cancer immunotherapy

  • Ann-Christin Franke,
  • Romain Hardet,
  • Lisa Prager,
  • Martin Bentler,
  • Mélanie Demeules,
  • Philipp John-Neek,
  • Nico Martin Jäschke,
  • Teng Cheong Ha,
  • Ulrich Thorsten Hacker,
  • Sahil Adriouch,
  • Hildegard Büning

Journal volume & issue
Vol. 29
pp. 238 – 253

Abstract

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Immunotherapy has significantly improved treatment outcomes in various cancer entities. To enhance immunogenicity and efficacy, and to further broaden its applicability, co-administration of anti-tumor vaccines is considered as a promising strategy. Here, we introduce adeno-associated virus (AAV) vectors, widely used for in vivo gene therapy, as a potent cancer vaccine platform. Our AAV vector-based vaccine combines antigen display on the capsid surface with a vector-mediated antigen overexpression targeting different components of the immune system in a unique chronological order by a single intramuscular application. Thereby, both profound and long-lasting antigen-specific T and B cell immune responses were induced. Moreover, mice receiving the vaccine were protected against tumor growth, demonstrating its efficacy in two tumor models, including the low immunogenic and aggressive B16/F10-Ova melanoma model. Remarkably, this approach was even effective in conditions of a late tumor challenge, i.e., 80 days post-vaccination, between 88% (B16/F10-Ova melanoma) and 100% (EG7 thymoma) of mice remained tumor free. Thus, decorating AAV vector particles with antigens by capsid engineering represents a potent vaccine concept for applications in cancer immunotherapy. Its modular and versatile ''plug-and-play'' framework enables the use of tumor antigens of choice and the easy implementation of additional modifications to enhance immunogenicity further.

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