Introduction:What they say:
A recent study from Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK shows that “Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.” This study was published in the 16 February 2016 issue of Immunity (one of the best journals in Immunology with an impact factor of 20+) by Prof Rudd CE, Taylor A and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Small molecule-based PD-1 pathway blockade for Human cancer therapy: Linagliptin, an inhibitor of dipeptidylpeptidase-4 (DPP-4), increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene
What is known?
It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year a few years ago.
This study suggests a small molecule-based Human cancer immunotherapy. Linagliptin (known by its trade names, such as BI-1356/Tradjenta) is used in the treatment of TIIDM.
The study presented here suggests that, Linagliptin, by decreasing the expression of its target gene, it may: (a) increase transcription factor T-bet expression; (b) inhibit co-inhibitory receptor PD-1 expression; (c) increase CD8(+) cytotoxic T lymphocyte function; (d) augment anti-tumor activity; & (e) inhibit metastatic cancer progression.
Thus, pharmacological formulations encompassing “Linagliptin or its analogues or Linagliptin plus any of the known anti-cancer agents” may be used to inhibit the progression of tumors.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
Undisclosed mechanistic information: How Linagliptin suppresses the expression of PD-1 and augments anti-tumor immunity
# Research cooperation
Citation: Boominathan, L., Small molecule-based PD-1 pathway blockade for Human cancer therapy: Linagliptin (brand name: BI-1356/Tradjenta), an inhibitor of dipeptidylpeptidase-4 (DPP-4), increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene, 3/January/2017, 5.12 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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