Journal of Glycobiology
Open Access

MUC1 glycopeptide based anti-cancer vaccines

Glycobiology World Congress

August 10-12, 2015 Philadelphia, USA

Sourav Sarkar

Scientific Tracks Abstracts: J Glycobiol

Abstract :

MUC1 variable number tandem repeats (VNTRs) conjugated to tumor-associated carbohydrate antigens (TACAs) have
been shown to break self-tolerance in humanized MUC1 transgenic mice. Therefore, we hypothesized that a MUC1
VNTR TACA-conjugate can be successfully formulated into a liposome-based anti-cancer vaccine. The immunogenicity of the
vaccine should be further augmented by incorporating surface displayed L-rhamnose (Rha) epitopes onto the liposomes to take
advantage of a natural antibody-dependent antigen uptake mechanism. To validate our hypothesis we synthesized a 20-amino
acid MUC1 glycopeptide containing a GalNAc-O-Thr (Tn) TACA by SPPS and conjugated it to a functionalized Toll-like receptor
ligand (TLRL). An L-Rha-cholesterol conjugate was prepared using Tetra Ethylene Glycol (TEG) as a linker. The liposomebased
anti-cancer vaccine was formulated by the extrusion method using TLRL-MUC1-Tn conjugate; Rha-TEG-cholesterol
and 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in a total lipid concentration of 30 mM. Groups of female BALB/c
mice were immunized and boosted with a rhamnose-Ficoll (Rha-Ficoll) conjugate formulated with alum as adjuvant to generate
the appropriate concentration of anti-Rha antibodies in the mice. The mice were then immunized with the TLRL-MUC1-Tn
liposomal vaccine formulated either with or without the surface displaying Rha epitopes. Sera collected from the groups of mice
initially immunized with Rha-Ficoll and later vaccinated with the Rha-displaying TLRL-MUC1-Tn liposomes showed a >8-fold
increase in both anti-MUC1-Tn and anti-Tn antibody titers in comparison to the groups of mice that did not receive Rha-Ficoll.
The anti-MUC1-Tn antibodies in the vaccinated mice serum also recognized MUC1 on human leukemia U266 cells.

Biography :

Sourav Sarkar has completed his PhD from University of Toledo and Postdoctoral studies from Complex Carbohydrate Research Center, University of Georgia.
Presently he is working as a Research Scientist III in the Department of Chemistry at Lehigh University. He has published numerous papers in reputed journals and
is an inventor of the patent “Xeno-antigenic anti-tumor vaccines”. He is a member of the American Chemical Society and has served as a peer reviewer for Elsevier,
Royal Society of Chemistry, Springer and many more journals.