Abstract 3563: CD8+ T cell-mediated tumor rejection by an Adeno-associated virus-like particle (AAVLP) vaccine

Abstract The utilization of adeno-associated viruses (AAVs) as vaccines has primarily been focused on the induction of antibody responses. Displaying antigens derived from HER2 or HPV on the AAV capsid surface lead to strong humoral immune responses. However, the potential of AAVs as T cell inducing vaccines has been poorly investigated. Model antigens have been inserted into the capsid of AAVs to analyze T cell responses, but these studies rather focused on preventing vector immunity for an improved tolerance of gene therapies. By using this as a starting point, we set out to test AAVs as T cell inducing vaccines with the prospect of targeting cancer neoantigens. In first experiments, the general properties of the vaccination strategy were estimated by displaying the ovalbumin-derived model antigen SIINFEKL on the surface of adeno-associated virus-like particles (AAVLPs). Upon injection of the AAVLP-SIINFEKL vaccine, mice developed strong CD8+ T cell responses against the displayed antigen. Highest immune responses were achieved by subcutaneous hock injection of AAVLPs, adjuvanted by Montanide ISA 51 VG. SIINFEKL-specific T cell responses peaked around three weeks after vaccination, whereas a memory subset remained present for long term. The anti-tumor efficacy of the vaccine was shown by injecting SIINFEKL-expressing B16F10 melanoma cells subcutaneously into mice, in which the tumor was completely rejected after vaccination. Interestingly, the induction of CD8+ T cell responses and the tumor protection depended on the presence of CD4+ T cells. Accordingly, T helper epitopes were identified in the AAVLP capsid sequence. In addition to the initial tests, a set of murine neoantigens, derived from B16F10 cells, were displayed on AAVLPs. In direct comparison to a peptide vaccine, which did not have an effect on tumor growth, the AAVLP vaccine had a significant impact on the tumor growth rate. In conclusion, AAVLPs show promising effects as T cell vaccines. The vaccination strategy can be used to induce cytotoxic T cell responses in general and anti-tumor effects in particular. AAV capsid-specific helper epitopes is one inherent advantage, since the AAVLP vaccine delivers immune stimulation within the viral particle itself. Thus, antigen-displaying AAVLPs could be an alternative to current gold standards in the field of neoantigen vaccines and have a prospect for future clinical applications. Citation Format: Lasse Neukirch, Patrick Schmidt, Inka Zörnig, Dirk Jäger, Silke Uhrig-Schmidt. CD8+ T cell-mediated tumor rejection by an Adeno-associated virus-like particle (AAVLP) vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3563.