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Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 8
May 14-15, 2018 | Montreal, Canada
Global Summit on
Biopharma & Biotherapeutics
T
umor associated carbohydrate antigens (TACAs)
are a class of glycans with important structural and
signaling functions playing a major role in cell proliferation,
differentiation, and apoptosis relevant to oncology. Tumor
cells expressing TACAs influence prognosis and survival of
cancer patients. We have used structure-based approaches
to study antigen-antibody interactions in the tumor micro-
environment and designed a peptidyl ligand that mimics the
molecular topology of TACAs even though they are chemically
dissimilar but functionally equivalent molecular structures.
Our work also suggests that in designing antibodies, careful
consideration should be made for somatic mutations that
enhance the rigidity of an antibody. Electrostatics play a
major role in the recognition of the model antigen examined.
Discrimination against wanted targets through repulsive
electrostatic interactions might be more fruitful than a
strong optimization of target binding whereas increased
specificity toward one target leads to decreased affinity
toward others. Models for TACA targeting reagents are
typified by TACA reactive monoclonal antibodies, lectins, and
perhaps oncolytic viruses that target sialylated receptors.
Peptides reactive with TACA may, in particular, be interesting
carbohydrate binding agents, forming the basis of novel
drugs that combine the advantages of antibodies and small
molecules. We have developed a peptidyl ligand that binds to
the TF or T antigen (Galβ1-3GalNAc). The designed peptidyl
ligand was observed functionally to mediate cell signaling of
TF expressing cell lines, suggesting that TF antigens might be
functionally interesting.
Speaker Biography
Somdutta Saha has completed her PhD degree in Bioinformatics from the University
of Arkansas at Little Rock in December 2013. She has investigated the developmental
pathway for antibodies reactive to neo-carbohydrate antigens expressed in several
metastatic cancers. She is interested in application of Bioinformatic approaches to
early stage drug discovery efforts. She was also selected as the first Early Talent Post-
doctoral Fellow in GlaxoSmithKline Plc., where she made significant contributions to
the understanding of host-microbe interactions via metabolite signaling. Currently, she
is a Staff Scientist at Duke Human Vaccines Institute in Durham, North Carolina involved
in designing better immunogens for HIV patients.
e:
sombioinfo@gmail.comTargeting the tumor associated carbohydrate antigens
Somdutta Saha
Duke Human Vaccine Institute, USA