On October 7, 2021 Second Genome, a biotechnology company that leverages its proprietary platform sg-4sight to discover and develop precision therapies and biomarkers, reported that preclinical data demonstrating that the Company’s novel microbiome-derived peptide, SG-3-0020, can upregulate key co-stimulatory and checkpoint molecules on T cells (Press release, Second Genome, OCT 7, 2021, View Source [SID1234590963]). The data (poster P260) were presented at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), held virtually on October 7-10, 2021.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Our findings that SG-3-0020 enhanced PD-1 expression and IFNg secretion by anti-CD3 activated human T cells in vitro provide a strong rationale for SG-3-0020’s potential future use in cancer therapies. Additionally, we are pleased to see these results provided additional validation of the advanced capabilities of sg-4sight, Second Genome’s proprietary platform, to identify targets for microbial peptides and proteins with potential therapeutic relevance in immuno-oncology," said Helena Kiefel, Ph.D., Head of Immuno-Oncology at Second Genome. "Given these promising preclinical data, we are looking to further develop SG-3-0020 with an experienced partner, as we continue to advance SG-3-00802, our lead immuno-oncology program for which we anticipate an IND submission in 2022 for SG-3-00802."
Using Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning tools, the Company analyzed the genome of Bifidobacterium (B.) breve and B. longum for proteins which were potentially secreted and had unknown functions. 50 peptides were chemically synthesized and then screened in cell-based assays for T cell activation and cytokine secretion.
SG-3-0020, a novel B. breve-derived 42-aa peptide, stimulated secretion of effector cytokines by in vitro-cultured T cells (IFNg, TNF-a, IL-10 and IL-2) and increased the expression of PD-1 on both CD4+ and CD8+ T cells when stimulated with low-dose anti-CD3 antibody. Mass spec analysis showed that SG-3-05308, a variant of SG-3-0020, binds to a transmembrane glycoprotein of the immunoglobulin superfamily. Silencing this gene via CRISPR-Cas significantly decreased PD-1 levels, cell proliferation and IFNg production in human pan T cells.
The potency of SG-3-0020 was further optimized for binding to activated T cells through protein engineering. The peptide with the highest potency, SG-3-05429, was selected for further investigation of the mechanism by which binding of its glycoprotein target results in activation of downstream T cell signaling pathways.
The poster presentation will be available for on-demand viewing on the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) website and will also be made available on the Company’s website at View Source