Outpace Bio to Present New Data on OutSmart™ IL-2/15, a CAR T Cell-Produced Designed Cytokine with Tumor-Localized Immune Cell Activity, at the 2023 Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT)
Seattle, WA, May 18, 2023 (GLOBE NEWSWIRE) — Outpace Bio, a company using protein design and cell engineering to create advanced cell therapies with curative potential, today announced it will present advancements to its OutSmartTM platform during a poster presentation at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual meeting being held from May 16-20, 2023 in Los Angeles, CA.
The data to be presented outline the latest advancements in Outpace’s proprietary OutSmartTM platform technology, which provides a way to exquisitely regulate cytokine signaling in the tumor microenvironment (TME), thereby overcoming a major barrier to efficacy for cell therapies in solid tumors by coordinating a productive immune response directly in the TME from both the engineered cell therapy as well as endogenous immune cells.
OutSmartTM bolsters cell signaling to treat solid tumors
Cancer cells, together with the immune cells that should be targeting them, produce signaling proteins that turn off the immune response creating a dysfunctional microenvironment that allows cancer to grow and spread. Pro-inflammatory cytokines could overcome the TME but pose a significant safety risk to patients when delivered systemically given their potency. Cell therapies engineered with OutSmart™ technology produce the right signals inside the tumor and keep them there. With OutSmart™, the cell therapy bolsters its own activity while also recruiting helpful bystander cells to achieve efficacy without compromising safety. OutSmart™ uses novel promoter elements to regulate gene expression and protein design to control which cells and signaling pathways are activated.
New data on OutSmartTM
The data to be presented demonstrate that the OutSmart™ platform can enhance CAR T cell function via a single vector genetic module that provides both IL-2 and IL-15 activity, preferentially expanding anti-tumor immune effector cells such as NK cells and CD8+ T cells, while minimizing Treg activation via ablation of IL-2Rα binding. Precise control via novel promoters achieves local secretion of OutSmart™ IL-2/15 to enhance CAR T cell proliferation and survival, stimulates immune effector cells in the TME, and reduces potential side effects associated with systemic IL-2 exposure. Antigen targeting provides additional control by retaining the cytokine near the tumor and addressing activity to specific cell populations.
“These OutSmart™ platform capabilities expand our ability to enable context-dependent, local delivery of cytokines to the TME to enhance CAR T cell function, promote bystander immune cell function, and reduce the risk of toxicity,” said Dr. Aaron Foster, PhD, Chief Scientific Officer. “We look forward to leveraging OutSmart™ IL-2/15 in both our internal T cell pipeline as well as in strategic collaborations with leading industry players. We are applying our OutSmart™ protein design expertise to create additional cytokines to achieve tumor-localized cytokine activity in a broad set of engineered cell types and cancers with high unmet need.”
Poster Presentation Details
Title: OutSmart™ IL-2/15: A CAR T Cell-Produced Designed Cytokine with Tumor-Localized Immune Cell Activity
Session Date/Time: Thursday, May 18, 2023
Abstract Number: 985 (available at: annualmeeting.asgct.org/abstracts)
Presenter: Dr. Aaron Foster, PhD, Chief Scientific Officer, at Outpace Bio
Abstract summary: CAR T cells have shown limited efficacy for the treatment of solid tumors due to poor persistence and an immune suppressive tumor microenvironment (TME). To overcome these barriers, we computationally designed OutSmartTM IL-2/15, which is engineered to minimize regulatory T cell (Treg) activation and to specifically engage and stimulate CD8+ immune effector cells (CD8+ T cells and NK cells). Our preclinical data demonstrate that designed OutSmartTM IL-2/15 cytokine preferentially stimulates CD8+ immune effector cells, including CD8+ T cells and NK cells, while minimizing the activation of immune suppressive regulatory T cells (Tregs). Through the discovery of novel gene expression promoters, we have subsequently developed integrated gene expression circuits that allow CAR T cells to produce OutSmartTM IL-2/15 in a context-dependent manner following recognition of tumor cells that drive CAR T proliferation and anti-tumor activity. By combining protein design with sophisticated cell engineering, we are able to construct genetic modules that can enhance CAR T cell function within the TME to preferentially expand CAR T cells and endogenous anti-tumor immune effector cells. More generally, OutSmartTM protein design and cell engineering may be applied to other immune modulating molecules to achieve tumor-localized activity for an improved efficacy and safety profile.
About Outpace Bio
Outpace is creating cell therapies with curative potential through protein design and cellular engineering. With an initial focus on solid tumors, Outpace is developing technologies that overcome the barriers to efficacy and safety by programming cells to make the right decisions inside patients. Outpace’s suite of technologies drive persistent activity of the cell therapy (OutLast™), recruit a productive immune response in the tumor microenvironment (OutSmart™), and achieve the potency (OutSpacers™), specificity (Co-LOCKR™), and safety (EGFRopt™) necessary to unlock diverse cancer indications. Outpace’s internal and partnered pipeline approach is optimized for rapid clinical validation of its technologies across diverse cell types and manufacturing processes. Outpace is based in Seattle, Washington. To learn more, visit outpacebio.com or email info@outpacebio.com and follow on Twitter and Instagram @OutpaceBio.
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