Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Apr;61(4):581-5.
doi: 10.1007/s00262-012-1205-9.

The entirely carbohydrate immunogen Tn-PS A1 induces a cancer cell selective immune response and cytokine IL-17

Affiliations

The entirely carbohydrate immunogen Tn-PS A1 induces a cancer cell selective immune response and cytokine IL-17

Ravindra A De Silva et al. Cancer Immunol Immunother. 2012 Apr.

Abstract

The tumor-associated carbohydrate antigen/hapten Thomsen-nouveau (Tn; a-D-GalpNAc-ONH2) was conjugated to a zwitterionic capsular polysaccharide, PS A1, from commensal anaerobe Bacteroides fragilis ATCC 25285/NCTC 9343 for the development of an entirely carbohydrate cancer vaccine construct and probed for immunogenicity. This communication discloses that murine anti-Tn IgG3 antibodies both bind to and recognize human tumor cells that display the Tn hapten. Furthermore, the sera from immunization of mice with Tn-PS A1 contain cytokine interleukin 17 (IL-17A), which is known to possess anti-tumor function and represents a striking difference to an IL-2, and IL-6 profile obtained with anti-PS A1 sera.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a Flow cytometry results using human tumor cell lines expressing the Tn hapten (2). Anti-sera (diluted at 1:250) from Tn-PS A1 (3)-primed C57BL/6 mice (red trace) and anti-sera (diluted at 1:250) from PS A1 (1)-primed C57BL/6 mice (blue trace) along with staining agent 2° IgG3 Ab conjugated with Alexa Fluor® 488 dye (green trace). FACS analysis shows Ab binding to MDA-231, MCF-7, Jurkat, JurkatTAg, and Panc-1 but not glioblastoma U251 (see discussion). PBMCs and bone marrow cells were used as controls. Results are representative of two replicate experiments. b Percentage of cells staining positive treated with sera from Tn-PS A1-inoculated animals compared with the percentage of cells staining with sera from PS A1 vaccinated animals. Percent of positive stained cells incubated with Tn-PS A1 sera were divided by those obtained from cells incubated with PS A1. Results represent the fold change from the average of two replicate experiments
Scheme 1
Scheme 1
The Tn-PS A1 construct (3) from the glycoconjugation of PS A1 (1) with Tn hapten (2)

References

    1. Avery OT, Goebel WF. Chemo-immunological studies on conjugated carbohydrate-proteins: II. Immunological specificity of synthetic sugar-protein antigens. J Exp Med. 1929;50:533–550. doi: 10.1084/jem.50.4.533. - DOI - PMC - PubMed
    1. Landsteiner K, van der Scheer J. On the influence of acid groups on the serological specificity of azoproteins. J Exp Med. 1927;45:1045–1056. doi: 10.1084/jem.45.6.1045. - DOI - PMC - PubMed
    1. Astronomo RD, Burton DR. Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat Rev Drug Discov. 2010;9:308–324. doi: 10.1038/nrd3012. - DOI - PMC - PubMed
    1. Galonic DP, Gin DY. Chemical glycosylation in the synthesis of glycoconjugate antitumor vaccines. Nature. 2007;446:1000–1007. doi: 10.1038/nature05813. - DOI - PMC - PubMed
    1. Velez CD, Lewis CJ, Kasper DL, Cobb BA. Type I streptococcus pneumonia carbohydrate utilizes a nitric oxide and MHC II-dependent pathway for antigen presentation immunology. 2009;127:73–82. - PMC - PubMed

Publication types

MeSH terms