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

  • NPJ Vaccines. 2022 Jun 23;7(1):64. doi: 10.1038/s41541-022-00484-y.
Elena Tondini  #  1 ,  Niels R M Reintjens  #  2 ,  Giulia Castello  1 ,  Tsolere Arakelian  1 ,  Marjolein Isendoorn  2 ,  Marcel Camps  1 ,  Jana Vree  1 ,  Gijs A van der Marel  2 ,  Dmitri V Filippov  2 ,  Jeroen D C Codee  3 ,  Ferry Ossendorp  4
Affiliations
  • 1. Department of Immunology, Leiden University Medical Center, Leiden University, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
  • 2. Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333, CC, Leiden, The Netherlands.
  • 3. Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333, CC, Leiden, The Netherlands. [email protected].
  • 4. Department of Immunology, Leiden University Medical Center, Leiden University, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands. [email protected].
  • # Contributed equally.
PMID: 35739113 DOI: 10.1038/s41541-022-00484-y
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.

Products