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Related Experiment Video

Updated: Jun 14, 2025

HLA-Ig Based Artificial Antigen Presenting Cells for Efficient ex vivo Expansion of Human CTL
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IOS-1002, a Stabilized HLA-B57 Open Format, Exerts Potent Anti-Tumor Activity.

Anahita Rafiei1, Marco Gualandi1, Chia-Lung Yang1

  • 1ImmunOs Therapeutics AG, 8952 Schlieren, Switzerland.

Cancers
|August 29, 2024
PubMed
Summary
This summary is machine-generated.

A novel fusion protein, IOS-1002, targets immune checkpoints to activate anti-tumor immunity. This human leukocyte antigen (HLA) molecule demonstrates efficacy in preclinical models, enhancing T and NK cell activity against cancer.

Keywords:
HLA open formatshuman leukocyte immunoglobulin-like receptorinnate checkpoint blockadekiller immunoglobulin-like receptor

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Area of Science:

  • Immunology
  • Oncology
  • Structural Biology

Background:

  • Human leukocyte antigen (HLA) class I molecules, specifically HLA-B27 and HLA-B57, are known for roles in autoimmunity and viral immunity.
  • Their involvement in cancer immunity, particularly interactions with innate immune checkpoint receptors like LILRB and KIR, is not well understood.

Purpose of the Study:

  • To investigate the role of HLA-B57 in cancer immunity.
  • To develop and characterize a novel fusion protein, IOS-1002, targeting immune checkpoints for anti-tumor activity.

Main Methods:

  • Engineered an open-format, stability-optimized HLA-B57-B2m-IgG4_Fc fusion protein (IOS-1002).
  • Assessed binding of IOS-1002 to LILRB1, LILRB2, and KIR3DL1.
  • Evaluated Fcγ receptor engagement, macrophage phagocytosis, and effects on immunosuppressive signaling pathways and cell differentiation.
  • Tested IOS-1002 efficacy in an ex vivo patient-derived tumoroid model.

Main Results:

  • IOS-1002 binds to LILRB1, LILRB2, and KIR3DL1.
  • The IgG4 Fc backbone mediates Fcγ receptor engagement and enhances macrophage phagocytosis.
  • IOS-1002 inhibits immunosuppressive signaling, reduces M2 macrophage polarization and myeloid-derived suppressor cell differentiation.
  • IOS-1002 enhances tumor cell phagocytosis, potentiates T and NK cell activation, and shows efficacy in a tumoroid model.

Conclusions:

  • IOS-1002 is a first-in-class, multi-target, and multi-functional HLA fusion protein.
  • It effectively activates anti-tumor immunity by modulating immune checkpoints and cellular responses.
  • IOS-1002 holds promise for cancer immunotherapy and is currently in clinical evaluation.