Targeting the CD58:CD2 axis for cancer immunotherapy

This technology is a cancer immunotherapy platform that activates CD28-CD8+ T-cells via the CD58:CD2 axis.

Unmet Need: Alternative avenues for patients insensitive to existing cancer immunotherapies

While the most effective immunotherapy current available uses anti-PD-1 antibodies to activate tumor CD8+ T-cells via the CD28 receptor, most cancer tumors have a large fraction of CD8+ T-cells without CD28, hindering these cells from responding to the therapy. To date, no therapies have been developed to specifically target these CD28-CD8+ T-cells to treat cancer.

The Technology: Activate CD28-CD8+ T-cells for cancer immunotherapy via the CD58:CD2 axis

This technology demonstrates the feasibility of stimulating the CD28-CD8+ T-cells for cancer immunotherapy by using the CD58:CD2 axis. CD58 is the ligand receptor for CD2, which is the most potent T-cell activator in the absence of CD28. CD58 is typically expressed on antigen presenting cells, and ablation of CD58 in cancer cells enhances PD-L1 signaling by releasing CMTM6, rendering the cells completely resistant to anti-tumor immunity. As such, targeting and disrupting CMTM6 regulation of PD-L1 protein using antibodies or by other means can enhance anti-tumor immunity alone or in combination with PD-1 blockade or adoptive cell transfer (ACT). These findings suggest that direct activation of CD2 using CD58 mimetics or antibodies is a potent cancer immunotherapy for patients unresponsive to the traditional anti-PD-1 antibody treatment.

This technology has been validated with humanized mouse models that express human CD58.

Applications:

  • Development of alternative cancer immunotherapy approaches
  • Development of alternative therapies for auto-immune disorders
  • Research tool for CD28-CD8+ T-cell activation
  • Research tool to study the role of CD58 in cancer and other diseases

Advantages:

  • Allows for activation of T-cells in patients not responsive to current cancer immunotherapy approaches
  • Describes alternative pathway to activate and regulate CD28-CD8+ T-cell activity
  • Provides humanized mouse model to study CD58 in murine models (as mice do not express CD58)

Lead Inventor:

Benjamin Izar, M.D., Ph.D.

Patent Information:

Patent Pending (WO/2022/132932)

Related Publications:

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