Natural product-derived PD-1 pathway blockade for Human cancer therapy: Vitalboside A, isolated from Syzygium cumini, decreases the activity of Glycogen synthase kinase-3β, 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, 12/April/2017, 8.09 am

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: 

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On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product-derived PD-1 pathway blockade for Human cancer therapy: Vitalboside A, isolated from Syzygium cumini, decreases the activity of Glycogen synthase kinase-3β, 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.

Research Findings: 

This study suggests a natural product-derived therapy for human cancers. Vitalboside A, by inhibiting the activity of Glycogen synthase kinase 3-β (fig 1), 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 (figs. 1-3)

Fig 1 Vitalboside A serves as an anti-tumor immunity booster. Vitalboside A increases T-bet expression, inhibits PD-1 expression, and augments anti-tumor immunity

Figure 2. Syzygium cumini

Figure 3. Syzygium cumini. Vitalboside A, found in Syzygium cumini, augments anti-tumor immunity via down regulation of PD-1

Therapeutic opportunity: 

Thus, pharmacological formulations encompassing “Vitalboside A  or its analogues either alone or in combination with other drugs“ 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/

Amount: $50

Undisclosed mechanistic information: How does  Vitalboside A suppress the expression of PD-1 to promote anti-tumor immunity?

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References:

Citation: Boominathan, L., Natural product-derived PD-1 pathway blockade for Human cancer therapy: Vitalboside A, isolated from Syzygium cumini, decreases the activity of Glycogen synthase kinase-3β, 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 genee, 12/April/2017,  8.08 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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