2. Academic Validation
  3. NKT cell-dependent glycolipid-peptide vaccines with potent anti-tumour activity

NKT cell-dependent glycolipid-peptide vaccines with potent anti-tumour activity

  • Chem Sci. 2015 Sep 1;6(9):5120-5127. doi: 10.1039/c4sc03599b.
Regan J Anderson 1,  Benjamin J Compton 1,  Ching-Wen Tang 2,  Astrid Authier-Hall 2,  Colin M Hayman 1,  Gene W Swinerd 2 3,  Renata Kowalczyk 4,  Paul Harris 4,  Margaret A Brimble 4 5,  David S Larsen 6,  Olivier Gasser 2,  Robert Weinkove 2 7,  Ian F Hermans 2 5 3,  Gavin F Painter 1
Affiliations

Affiliations

  • 1 The Ferrier Research Institute , Victoria University of Wellington , PO Box 33436 , Lower Hutt 5046 , New Zealand . Email: [email protected].
  • 2 Malaghan Institute of Medical Research , PO Box 7060 , Wellington 6242 , New Zealand . Email: [email protected].
  • 3 School of Biological Sciences , Victoria University of Wellington , PO Box 600 , Wellington 6140 , New Zealand.
  • 4 School of Biological Sciences , The University of Auckland , 3 Symonds St , Auckland Central , 1142 , New Zealand.
  • 5 Maurice Wilkins Centre for Molecular Biodiscovery , The University of Auckland , 3 Symonds St , Auckland Central , 1142 , New Zealand.
  • 6 Department of Chemistry , University of Otago , PO Box 56 , Dunedin 9054 , New Zealand.
  • 7 Department of Pathology & Molecular Medicine , University of Otago Wellington , New Zealand.
PMID: 28717498 DOI: 10.1039/c4sc03599b
Abstract

It is known that T cells can eliminate tumour cells through recognition of unique or aberrantly expressed antigens presented as peptide epitopes by major histocompatibility complex (MHC) molecules on the tumour cell surface. With recent advances in defining tumour-associated antigens, it should now be possible to devise therapeutic vaccines that expand specific populations of anti-tumour T cells. However there remains a need to develop simpler efficacious synthetic vaccines that possess clinical utility. We present here the synthesis and analysis of vaccines based on conjugation of MHC-binding peptide epitopes to α-galactosylceramide, a glycolipid presented by the nonpolymorphic antigen-presenting molecule CD1d to provoke the stimulatory activity of type I natural killer T (NKT) cells. The chemical design incorporates an enzymatically Cleavable Linker that effects controlled release of the active components in vivo. Chemical and biological analysis of different linkages with different enzymatic targets enabled selection of a synthetic vaccine construct with potent therapeutic anti-tumour activity in mice, and marked in vitro activity in human blood.

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