NKT-cells ligands enhance oral cancer vaccine efficiency

Current cancer vaccine strategies strive to efficiently deliver in situ immunogenic Tumour-Associated Antigens (TAAs) into  functional Antigen-Presenting Cells (APCs).  Stimulated APCs cells then initiate anti-tumour reactions through local and complex immune interactions targeting also the tumour microenvironment.

In this context, Xu et al. have recently developed a new effective oral cancer vaccine platform presenting potent immunogenicity and anti-tumour activity with long-lasting protective memory response (1).

Alpha-Gal-Cer interactions with AP cells and its adjuvant effect

Schematic representation of the role of KRN7000 in linking innate and adaptive immunities through the interaction between dendritic cells (DCs)and NKT cells. Source: Alphagalcer.net and RIKEN RCAI.

The authors have designed optimized Salmonella-based vectors (Salmonella SPI2-encoded T3SS system) co-administrated with a Natural Killer (NKT) cells ligand (2). The delivery of heterogeneous TAAs into APCs has been proven to display enhanced anti-tumour activity through bacterial expressed TAAs-specific immune reponses.

Chemically synthesized NKT cells ligands (alpha-Galactosylceramide known as the αGalCer KRN7000) and its superior binding affinity analog 7DW8-5 were already known to enhance the immunogenicity and anti-tumour efficacy of bacterial vaccine vectors (3, 4).

Xu et al. clearly show here the potential interest of 7DW8-5 as a vaccine adjuvant in clinical tumour treatment with oral vaccines.

Sources:

  1. Xu et al. “Development of an Effective Cancer Vaccine Using Attenuated Salmonella and Type III Secretion System to Deliver Recombinant Tumor-Associated Antigens” (2014) Cancer Res Published Online First September 11, 2014. DOI:10.1158/0008-5472.CAN-14-1169.
  2. Nicol A. et al. “Comparison of clinical and immunological effects of intravenous and intradermal administration of a-galactosylceramide (KRN7000)-pulsed dendritic cells” (2011) Clin Cancer Res, 1;17(15):5140-51. DOI: 10.1158/1078-0432.CCR-10-3105.
  3. Xiong G. et al. “Novel cancer vaccine based on genes of Salmonella pathogenicity island 2” (2010) Int J Cancer,126:2622-34. DOI: 10.1002/ijc.24957.
  4. Li X. et al. “Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant” (2010) Proc Natl Acad Sci U S A 2010;107:13010-5. DOI: 10.1073/pnas.1006662107.

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