P09.03 Hyaluronic acid as a new immunologic adjuvant in cancer: design of effective preventive and therapeutic vaccination strategies for HER2/neu-positive breast tumors

Background The use of proteins as immunogens is attractive for the development vaccines, but requires efficient adjuvants to overcome their weak immunogenicity. Recently, we investigated potential TLR2/4 agonist hyaluronan (HA) an immunological adjuvant protein-based vaccines. 1 2 Conjugation HA antigens strongly increased immunogenicity and promoted rapid translocation draining lymph nodes, resulting in robust long-lasting humoral responses. On these bases, potentiality HA-based technology design cancer To this aim, was conjugated extracellular domain rat HER2/neu (rHER2/neu) validated preventive therapeutic vaccination settings. Materials Methods Female BALB/c or BALB-neuT mice were immunized with rHER2/neu-HA. In vivo depletion CD4 + , CD8 T B cells performed, sera spleens collected characterized antigen-specific cellular Vaccinated challenged re-challenged rHER2/neu-overexpressing TUBO assess protective activity rHER2/neu-HA strategy, well memory. Results performed efficiently (IgG1, IgG2a, IgG2b) responses detected using very low antigen doses number boosters. Outstandingly, at 1-year post-vaccination, anti-rHER2/neu specific antibodies showed even improved effector functions (maturation affinity receptor complement-derived cytotoxicity functions). turned out effective both prophylactic (100% survived) (tumor regression 2/12 mice) settings, broke tolerance against rHER2/neu, delaying spontaneous tumor growth mice. Both contributed success vaccination, played only a marginal role. Conclusions Cancer vaccines have not yet achieved significant clinical efficacy due poor immunogenicity, validation more occurred sometimes expense safety. combines unique immunomodulatory features TLR tolerability fully natural polymer, proving be promising creation safe translation. References Dalla Pietà A, Carpanese D, et al . Hyaluronan Cell Mol Immunol 2021; 18 (5):1197–1210. Rosato Montagner IM, A. Hyaluronic acid protein peptide-based 30.04.2020. WO/2020/084558, PCT/IB2019/059122. Disclosure Information D. Carpanese: None. I. Montagner: Pietà: V. Rossi: Penna: G. Zuccolotto: Pasut: Grigoletto: Rosato: