PORT-5 / Stimunity, AlphaTON Capital - LARVOL DELTA

A dendritic cell autophagy-neutrophil axis limits intratumoral STING immunotherapy. (PubMed, Sci Immunol) - "STING-induced type I interferon signaling was dispensable for cGAMP-VLP-mediated tumor control...Neutrophil depletion enhanced tumor control through mechanisms involving neutrophil elastase and programmed cell death 1 ligand 1. These findings reveal that defective dendritic cell autophagy and neutrophil-mediated immunosuppression, rather than insufficient interferon signaling, hinder the effectiveness of intratumoral STING immunotherapy in preclinical mouse models."

Journal • Oncology • CD8 • CGAS • ELANE • PD-1 • PD-L1 • STING

STING Activation in Dendritic Cells Enhances Antigen Presentation by Live Tumor Cells. (PubMed, Eur J Immunol) - "In vivo, host STING activation with cGAMP-VLP improves the efficacy of immune checkpoint blockade, particularly in tumors lacking cGAS. Together, these findings identify a transcellular mechanism whereby STING activation in dendritic cells increases tumor cell MHC-I expression to enhance CD8+ T cell-mediated tumor recognition."

Journal • Oncology • CD8 • STING

Selective STING stimulation in dendritic cells primes antitumor T cell responses. (PubMed, Sci Immunol) - "By contrast, intratumoral injection of the synthetic CDN ADU-S100 led to tumor necrosis and systemic T cell activation but simultaneously depleted immune cells from injected tumors and induced minimal priming of circulating tumor-specific T cells. Subcutaneous administration of cGAMP-VLP showed synergy when combined with PD1 blockade or a tumor T-depleting antibody to elicit systemic tumor-specific T cells and antitumor activity, leading to complete and durable tumor eradication in the case of tumor T depletion. These findings show that cell targeting of STING stimulation shapes the antitumor T cell response and identify a therapeutic strategy to enhance T cell-targeted immunotherapy."

Journal • Oncology • STING

"$PRTG @StimunityBio Nice mention on PORT-2 & PORT-5" (,@jamvest20)

Cellular selectivity of STING stimulation determines priming of anti-tumor T cell responses (AACR 2022) - "Sub-cutaneous administration of cGAMP-VLP showed synergy when combined with a tumor Treg-depleting antibody to elicit systemic tumor-specific T cells, leading to complete and lasting tumor eradication. These findings show that cell targeting of STING stimulation shapes the anti-tumor T cell response and reveal a therapeutic strategy with T cell modulators, which may address the current limitations of STING-based approaches in patients."

Late-breaking abstract • Oncology • STING

Portage Biotech Highlights Promising Data Presented on STING-Activating Therapy, PORT-5 (STI-001) at AACR 2022 Annual Meeting (GlobeNewswire) - "Preclinical data shows that PORT-5 (STI-001), a stimulator of interferon genes (STING) agonist, cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) packaged in a virus-like particle (VLP) developed with Stimunity, can be delivered systemically and achieve potent activation of the STING pathway preferentially in dendritic cells. The data will be presented in a late-breaking research session at the AACR meeting on Wednesday, April 13."

Late-breaking abstract • Preclinical • Oncology

Portage Biotech Announces Presentation of PORT-5 (STI-001) Late-Breaking Data at AACR 2022 Annual Meeting (GlobeNewswire) - "Portage Biotech...and Stimunity...announced data from a collaboration on a STING-activating therapy, PORT-5 (STI-001) will be presented at the American Association for Cancer Research (AACR) 2022 Annual Meeting taking place April 8-13, 2022, in New Orleans, Louisiana....Preclinical data will be presented in a late-breaking abstract session."

Late-breaking abstract • Preclinical • Oncology