Shattuck Labs
  • About
    • Overview
    • Our Origins
    • Mission & Vision
    • Management
    • Board of Directors
    • Advisory Board
  • Our Science
    • ARC Platform
    • GADLEN Platform
    • Posters
    • Publications
  • Pipeline
    • Clinical
    • SL-172154 SIRPα-Fc-CD40L
    • Discovery
  • Clinical Trials
    • Overview
    • SL-172154
      • Ovarian Cancer
      • AML & HR-MDS
  • Investors
    • Overview
    • News & Events
      • Press Releases
      • Events & Presentations
    • Stock Info
      • Stock Quote & Chart
      • Analyst Coverage
    • Financials
      • SEC Filings
      • Quarterly Results
    • Governance
      • Documents & Charters
      • Management Team
      • Board of Directors
      • Committee Composition
    • IR Resources
      • FAQS
      • Email Alerts
      • IR & Media Contact
  • Careers
    • Intro to Shattuck
    • Values
    • Benefits
    • Join Our Team
    • Current Openings
  • Contact
    • Locations
    • Contact Us

Our Science

Suresh de Silva, George Fromm, Casey W Shuptrine, Kellsey Johannes, Arpita Patel, Kyung Jin Yoo, Kaiwen Huang and Taylor H Schreiber

Abstract for – CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade, Bridging Innate and Adaptive Immunity

Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody dependent cellular phagocytosis (ADCP) of targeted antibodies. Pre-clinically, CD47/SIRPα blockade induces antitumor activity by increasing the phagocytosis of tumor cells by macrophages and enhancing the cross-presentation of tumor antigens to CD8+ T cells by dendritic cells; both of these processes are potentiated by CD40 signaling. Here we generated a novel, two-sided fusion protein incorporating the extra cellular domains of SIRPα and CD40L, adjoined by a central Fc domain, termed SIRPα-Fc-CD40L. SIRPα-Fc-CD40L bound CD47 and CD40 with high affinity and activated CD40 signaling in the absence of Fc receptor cross-linking. No evidence of hemolysis, hemagglutination or thrombocytopenia was observed in vitro or in cynomolgus macaques. Murine SIRPα-Fc-CD40L outperformed CD47 blocking and CD40 agonist antibodies in murine CT26 tumor models and synergized with immune checkpoint blockade of PD1 and CTLA4. SIRPα-FcCD40L activated a type I interferon response in macrophages and potentiated the activity of ADCP-competent targeted antibodies both in vitro and in vivo. These data illustrated that whereas CD47/SIRPα inhibition could potentiate tumor cell phagocytosis, CD40-mediated activation of a type I interferon response provided a bridge between macrophage and T cell mediated immunity that significantly enhanced durable tumor control and rejection  

  • About
  • Our Science
  • Pipeline
  • Clinical Trials
  • Investors
  • Careers
  • Contact
© 2023 Shattuck Labs, Inc | Privacy | Terms of Use
logo
  • About
    • Overview
    • Our Origins
    • Mission & Vision
    • Management
    • Board of Directors
    • Advisory Board
  • Our Science
    • ARC Platform
    • GADLEN Platform
    • Posters
    • Publications
  • Pipeline
    • Clinical
    • SL-172154 SIRPα-Fc-CD40L
    • Discovery
  • Clinical Trials
    • Overview
    • SL-172154
      • Ovarian Cancer
      • AML & HR-MDS
  • Investors
    • Overview
    • News & Events
      • Press Releases
      • Events & Presentations
    • Stock Info
      • Stock Quote & Chart
      • Analyst Coverage
    • Financials
      • SEC Filings
      • Quarterly Results
    • Governance
      • Documents & Charters
      • Management Team
      • Board of Directors
      • Committee Composition
    • IR Resources
      • FAQS
      • Email Alerts
      • IR & Media Contact
  • Careers
    • Intro to Shattuck
    • Values
    • Benefits
    • Join Our Team
    • Current Openings
  • Contact
    • Locations
    • Contact Us
  • Follow Us