vaccines-gynecologic-oncology-2018-posters

Page 100

Journal of Clinical Immunology and Allergy

ISSN: 2471-304X

E u r o p e a n C o n g r e s s o n

Vaccines & Vaccination

and Gynecologic Oncology

Vaccines & Vaccination and Gynecologic Oncology 2018

O c t o b e r 2 6 - 2 7 , 2 0 1 8

B u d a p e s t , H u n g a r y

ancer-associated mucin glycoprotein MUC1 is characterized by the presence of altered carbohydrates such as Tn (α-N-

acetylgalactosamine), sTn (sialyl-1-6-Tn) and the Thomsen-Friedenreich (TF: β-D-Galp-1-3-α-D-GalNAcp) antigen (tumor

associated carbohydrate antigens: TACAs) that are conjugated to proteins via O-α-galactosylation of serine or/and threonine.

Patients immunized with synthetic TF conjugated with KLH (keyhole limpet hemocyanin) + QS21 adjuvant can generate IgM and

IgG antibodies because, the disaccharide TF is hydrolyzed rapidly in the body, strong immune response requires longer lived

disaccharides. Fluororinated TACAs have been proposed which elicit IgG antibodies found to cross-react with native TF epitopes.

We have found that the C-linked disaccharide analogue 1 (constructed applying Danishesky's method for the conjugation with

KLH) + QS21 adjuvant induces a strong immune response in mice. Interestingly, much weaker immune response was observed

with a stereoisomeric antigen constructed with the α-C-galactoside analogue of TF disaccharide (α-D-Galp-1-CH2-3-α-D-GalNAc-

O-Ser). Several strategies and methods have been developed for the synthesis of C-linked disaccharides including disaccharide

mimetics incorporating iminosugars C-linked to sugars and sugar mimetics such as conduritols and cyclitols. The latter work was

motivated by the search for specific glycosidase and glycosyltransferase inhibitors that are potential drugs against cancers and

other diseases.

Disaccharide mimetics as drugs against cancer and

epitopes for anti-cancer vaccine candidates

Loay Awad and Pierre Vogel

Swiss Institute of Technology in Lausanne (EPFL), Switzerland

Journal of Clinical Immunology and Allergy, Volume: 4

DOI: 10.21767/2471-304X-C2-006

Euro Vaccines 2018