- Facts shown that AAV vectors expressing engineered immunomodulatory interferon (IFN) cytokine payloads led to:
- Speedy and selective reduction in tumor size in significant-grade glioma (HGG) organoids
- Tumor regression and noticeably extended survival in 450 treated mice across 3 field top HGG human xenograft and allograft mouse versions
- Prevalent tumor mobile loss of life by means of apoptosis inside 48 hours of cure
- Reproducible tumor eradication, no evidence of residual proliferating tumor cells, and no evidence of cytokine payload expression by Day 7 publish-procedure
- Siren officially released out of stealth nowadays, coinciding with today’s ASGCT presentation
SAN FRANCISCO, May possibly 17, 2023 (Globe NEWSWIRE) — Siren Biotechnology now introduced the presentation of preclinical info demonstrating the effect of a novel therapy for most cancers, Common AAV Immuno-Gene Therapy, which brings together AAV gene treatment and cytokine immunotherapy into a one modality. The oral presentation titled, “AAV immuno-gene treatment provides vectorized cytokines to correctly address high-grade gliomas,” will be specified by renowned AAV gene treatment expert and Siren’s Founder and Main Government Officer, Nicole Paulk, PhD, at 3:45pm PT at the ASGCT 26th Once-a-year Assembly, having position in Los Angeles, Could 16-20th. Dr. Paulk will explain how this exact and extremely specific method signifies a novel system for destroying tumor cells and eliciting anti-tumor immunity. Backlink in this article to overview Siren’s ASGCT summary and here to assessment the company’s launch press release also issued this morning.
The Siren team performed many experiments to consider the security and efficacy of an immuno-gene therapy that utilizes AAV9 vectors expressing 12 unique engineered immunomodulatory interferon (IFN) cytokine payloads comprising IFNɑ1, IFNβ, IFNƔ, and combinations thereof.
- In principal human superior-quality glioma (HGG) organoids, Siren’s AAV immuno-gene therapies promptly and selectively lowered tumor size. In comparison, phosphate buffered saline, dimethyl sulfoxide diluent, and AAV9-GFP (inexperienced fluorescent protein) had no outcome on tumor or healthy cerebral cells in HGG organoids, and HGG tumor cells grew uncontrollably. Temozolomide chemotherapy, the latest common of care for HGG, noticeably decimated wholesome cerebral cells and only a bit delayed HGG tumor progress.
- In vivo knowledge demonstrated that AAV immuno-gene therapies effectively decreased tumor stress in a few HGG mouse designs that received intratumoral administration of the cytokine payloads through convection-increased supply (CED). Therapy with AAV immuno-gene therapies resulted in tumor regression and significantly prolonged survival in human GBM6 xenografts (P<0.2-0.001 and 31 – 60% complete responses (CRs)) mouse GL261 allografts (P<0.0009) and human patient-derived xenografts (P<0.04 30% CR) n=450.
- An evaluation of tumor-bearing mouse brains demonstrated marked tumor changes following treatment with AAV immuno-gene therapies. Within 48 hours following treatment, local intratumoral expression of Siren’s engineered IFNs had already led to widespread tumor cell apoptosis, and activation of brain-resident macrophages known as microglia, a class of antigen-presenting immune cells that specialize in clearing necrotic and apoptotic cells. By Day 7, there was reproducible tumor eradication, no evidence of residual proliferating cells, no remaining engineered cytokine payload expression, and only residual microglial activity.
- Subsequent single cell sequencing on syngeneic mouse brain tumors following AAV immuno-gene therapy treatment showed that tumor cells exhibited a significant upregulation of genes linked to IFN responses, as well as other classic immune response genes. These responses were specific to IFN payload expression and not AAV.
“We’re excited to present these potentially transformative data as we simultaneously introduce Universal AAV Immuno-Gene Therapy and Siren Biotechnology,” said Dr. Paulk. “This novel approach represents a new, big, bold idea to fight cancer by combining the potential of AAV gene therapy and cytokine immunotherapy into a single modality. Our vision is for Universal AAV Immuno-Gene Therapy to become the standard of care for any solid tumor cancer. Bolstered by the results shared today at ASGCT, we’ve started our vision-led journey with an initial focus on brain and eye cancers. Attempts to treat these cancers with systemic drugs have largely failed. The unmet need for these patients is dire, and our opportunity to help is massive.”
About Siren Biotechnology
Headquartered in San Francisco, CA, Siren Biotechnology is sounding the alarm against cancer. We are pioneers of Universal AAV Immuno-Gene Therapy™, which combines the promise of two transformative therapeutic technologies, AAV gene therapy and cytokine immunotherapy, into a single modality to redefines how we destroy tumor cells and elicit anti-tumor immunity. Our vision is for Universal AAV Immuno-Gene Therapy to become the standard of care for any solid tumor cancer.
To learn more about Siren and opportunities to join our team, visit sirenbiotechnology.com, and follow us on LinkedIn and Twitter.
Universal AAV Immuno-Gene Therapy for Cancer. It’s Here.
Photos accompanying this announcement are available at