Lipid A analog CRX-527 conjugated to synthetic peptides enhances vaccination efficacy and tumor control

Tondini, E.; Reintjens, N.R.M.; Castello, G.; Arakelian, T.; Isendoorn, M.; Camps, M.; ... ; Ossendorp, F. (2022)

Article / Letter to editor

Adjuvants play a determinant role in cancer vaccination by optimally activating APCs and shaping the T cell response. Bacterial-derived lipid A is one of the most potent immune-stimulators known, and is recognized via Toll-like receptor 4 (TLR4). In this study, we explore the use of the synthetic, non-toxic, lipid A analog CRX-527 as an adjuvant for peptide cancer vaccines. This well-defined adjuvant was covalently conjugated to antigenic peptides as a strategy to improve vaccine efficacy. We show that coupling of this TLR4 agonist to peptide antigens improves vaccine uptake by dendritic cells (DCs), maturation of DCs and T cell activation in vitro, and stimulates DC migration and functional T cell priming in vivo. This translates into enhanced tumor protection upon prophylactic and therapeutic vaccination via intradermal injection against B16-OVA melanoma and HPV-related TC1 tumors. These results highlight the potential of CRX-527 as an adjuvant for molecularly defined cancer vaccines, and support the design of adjuvant-peptide conjugates as a strategy to optimize vaccine formulation.

• All authors: Tondini, E.; Reintjens, N.R.M.; Castello, G.; Arakelian, T.; Isendoorn, M.; Camps, M.; Vree, J.; Marel, G.A. van der; Filippov, D.V.; Codee, J.D.C.; Ossendorp, F.
• Date: 2022-06-23
• Journal: npj Vaccines
• Volume: 7
• Issue: 1
• DOI: doi:10.1038/s41541-022-00484-y