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NIH grant 1R43AI192073-01A1: Development of an immunotherapeutic agent for treatment of osteomyelitis
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Stephanie Mack. Award: $320863.
Start: 2026-08-21T00:00:00.
Summary
Osteomyelitis is an inflammation of bone tissue, often caused by an infection with Staphylococcus aureus (S.
aureus). This condition can arise after trauma, during bacteremia, or following surgery, making it a potential risk
for anyone. Diabetics are especially prone vulnerable, due to the high occurrence of infected foot ulcers. S.
aureus infection depletes and exhausts cytotoxic CD8 T-cells, creating an immunosuppressive environment that
allows bacteria to thrive. The immune system is closely connected to the skeletal system, with cytokines, growth
factors, and immune cells playing essential roles in bone development, remodeling, and repair. Interleukin-2 (IL-
2) is a crucial cytokine used in clinical settings for over 40 years, but its widespread therapeutic use is limited
due to significant toxicity. IL-2 modulates the immune response by selectively activating both immune-stimulating
cytotoxic CD8 T-cells and NK cells, as well as immunosuppressive regulatory T-cells, through different receptor
binding affinities. This dual affinity is the main cause of its toxicity. Attempts to engineer IL-2 to favor the activation
of immunostimulatory cells have faced challenges due to weak receptor binding. We are developing CM-HZ01,
a high-avidity IL-2 super agonist designed to preferentially promote the expansion of cytotoxic CD8 and NK cells.
In this Phase I application, we aim to streamline CM-HZ01 production, demonstrate its ability to expand cytotoxic
lymphocytes under bacterial challenge, and treat osteomyelitis in a rodent model while promoting healthy bone
growth.document fetched 2026-08-30 02:46