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Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model

Stannard, Kimberley A. ; Collins, Patrick M. ; Ito, Koichi ; Sullivan, Emily M. ; Scott, Stacy A. ; Gabutero, Elwyn ; Darren Grice, I. ; Low, Pauline ; Nilsson, Ulf J. LU and Leffler, Hakon LU , et al. (2010) In Cancer Letters 299(2). p.95-110
Abstract

High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8+ CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory... (More)

High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8+ CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Disaccharides, Galectin-1 inhibitor, Tumour immunity, T-cells
in
Cancer Letters
volume
299
issue
2
pages
16 pages
publisher
Elsevier
external identifiers
  • wos:000284977000002
  • scopus:78049310747
  • pmid:20826047
ISSN
1872-7980
DOI
10.1016/j.canlet.2010.08.005
language
English
LU publication?
yes
id
002718d5-15ae-4242-a12f-a8fffb9c4c0b (old id 1751967)
date added to LUP
2016-04-01 12:58:55
date last changed
2023-05-15 07:43:40
@article{002718d5-15ae-4242-a12f-a8fffb9c4c0b,
  abstract     = {{<p>High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8<sup>+</sup> CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.</p>}},
  author       = {{Stannard, Kimberley A. and Collins, Patrick M. and Ito, Koichi and Sullivan, Emily M. and Scott, Stacy A. and Gabutero, Elwyn and Darren Grice, I. and Low, Pauline and Nilsson, Ulf J. and Leffler, Hakon and Blanchard, Helen and Ralph, Stephen J.}},
  issn         = {{1872-7980}},
  keywords     = {{Disaccharides; Galectin-1 inhibitor; Tumour immunity; T-cells}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{95--110}},
  publisher    = {{Elsevier}},
  series       = {{Cancer Letters}},
  title        = {{Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model}},
  url          = {{http://dx.doi.org/10.1016/j.canlet.2010.08.005}},
  doi          = {{10.1016/j.canlet.2010.08.005}},
  volume       = {{299}},
  year         = {{2010}},
}