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

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.

• Authors: 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
• Journal: NPJ vaccines (NPJ Vaccines) Vol. 7 Issue 1 Pg. 64 (Jun 23 2022) ISSN: 2059-0105 [Electronic] England
• PMID: 35739113 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).