Saturday Seminar - Evolution of Biopharmaceuticals

Seminar on Evolution of Biopharmaceuticals using Cell-SELEX and Phage-Display Technology.

 

Name of Speaker : Dr. Swapnil Sinha
                               Associate Professor
                               Department of Biochemistry
                               Assam Down Town University

 

Date of Presentation: 22/09/2018

Summary:

The major impediment in curing Cancer is the involvement of multiple number of
intracellular factors/protein players in the manifestation of this disease. This hurdle leaves
scientists with the alternative of targeting housekeeping proteins like Topoisomerase, to kill
the cell, which is in no way specific to the cancer cell and results in an array of side effects,
which are fatal at times. A better way to kill the targeted cancer cells could be to
activate/recruit the host immune response by the bound antibody. Cell-SELEX (Systemic
Evolution of Ligands by Exponential Enrichment) and Biopanning using Phage display
technology has emerged as promising methods to evolve DNA and peptide Aptamers that
can specifically bind to cancer cells without exhibiting any affinity to normal cells. The
present talk outlines the procedures involved to generate DNA and peptide Aptamers using
cell-SELEX and phage display technology. The ability to generate highly specific Aptamers
identifying specific cell types shows great potential in the development of cell-based
diagnostics and therapeutics. Evolved nucleic acid Aptamers have gained vast application in
cancer therapy and there are definitely several merits over existing conventional drug
therapies. One major advantage of Aptamers is that they can be chemically modified and
they can still retain their full functionality. We exploit this capability of Aptamers by
chemically conjugating the selected Aptamers with Di-Nitro Phenol (DNP). DNP is a ‘Hapten’
which does not evoke any immune response when administered alone but when it is
conjugated to any ‘carrier molecule’ it is highly immunogenic. They conjugated a small
organic molecule having specificity to a surface antigen. Acute myeloid leukemia is the
cancer of blood where there is an abnormal proliferation of White Blood Cells (WBCs), if
there is a mechanism where these abnormal WBCs are tagged and eliminated from the
circulation then it might become a very potent immunotherapeutic. We conceptualize that
when in vitro evolved Leukemic cell specific Aptamer conjugated with DNP is administered to in
vivo mouse xenograft leukemia models, the Aptamer will specifically identify and bind leukemic
cells and Hapten DNP will induce immune response specific to cells bound by Aptamers. The
natural antibodies produced against cancer cell-Aptamer-DNP complex will activate the
membrane attack complex (MAC) and will lead to immune-mediated toxicity to cancer cells and
ultimately to apoptosis. We envisage that DNA/peptide based therapy could be the game
changing approach for targeted anti-cancer immunotherapy and will form a template for
developing potent and cost effective therapeutics.

 



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