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

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.

Adeno-Associated Virus Vector Design-Moving the Adeno-Associated Virus to a Bioengineered Therapeutic Nanoparticle.

Although the number of market-approved gene therapies is still low, this new class of therapeutics has become an integral part of modern medicine. The success and safety of gene therapy depend on the vectors used to deliver the therapeutic material. Adeno-associated virus (AAV) vectors have emerged as the most frequently used delivery system for in vivo gene therapy. This success was achieved with first-generation vectors, using capsids derived from natural AAV serotypes. Their broad tropism, the high seroprevalence for many of the AAV serotypes in the human population, and the high vector doses needed to transduce a sufficient number of therapy-relevant target cells are challenges that are addressed by engineering the capsid and the vector genome, improving the efficacy of these biological nanoparticles.