npj Vaccines (Jun 2022)

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

  • Elena Tondini,
  • Niels R. M. Reintjens,
  • Giulia Castello,
  • Tsolere Arakelian,
  • Marjolein Isendoorn,
  • Marcel Camps,
  • Jana Vree,
  • Gijs A. van der Marel,
  • Dmitri V. Filippov,
  • Jeroen D. C. Codee,
  • Ferry Ossendorp

DOI
https://doi.org/10.1038/s41541-022-00484-y
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 11

Abstract

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Abstract 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.