This technology identifies multiple targetable pathways involved in radiation therapy-driven induction of immunosuppressive myeloid cells.
Unmet Need: Enhanced efficacy of radiation-based cancer therapies
Current treatments for many solid tumors, including radiation therapy, can stimulate the production of immunosuppressive myeloid cells. Increased abundance of these cell types is associated with poor prognosis in cancer patients. There are currently no systemic immunotherapies designed and approved for combination with radiation therapy, Therefore, inhibition of immunosuppressive myeloid cells is a promising target for enhancing the efficacy of radiation-based cancer therapies.
The Technology: Inhibition of immunosuppressive myeloid cells by pathway-specific targeted therapy
This technology identifies several targetable pathways involved in radiation therapy-driven induction of immunosuppressive myeloid cells. These pathways were validated using small molecule and antibody-driven pathway manipulations and transgenic mouse models, then further validated in humans with irradiated and unirradiated human pancreatic cancer samples using single-cell sequencing technology and CITE-Seq. High-throughput screenings will identify small molecule inhibitors of these pathways. A myeloid-directed immunotherapy combined with radiation therapy has the potential to improve cancer-specific outcomes for patients with solid tumors.
This technology has been validated in a preclinical mouse model and human pancreatic tissues.
Applications:
- Inhibition of immunosuppressive myeloid cells for treatment of cancer and viral infections
- Curative treatment of oligometastatic cancers
- Research model for studying myeloid cell migration, immunosuppression, and differentiation
- Research model for delineating subtypes of myeloid cells
- Research assay for tumor drug discovery
- Disease diagnostic for cancer patients
- Predictive modeling for disease progression
Advantages:
- Can be used alone or in combination with current standards of care: immunotherapy, chemotherapy, and radiation therapy, to improve patient outcomes
- Targets identified could improve efficacy of cancer treatment by suppressing specific cell types
- Increases effectiveness of disease diagnostics for patients by assessing myeloid subtypes
Lead Inventor:
Catherine Spina, M.D., Ph.D.
Related Publications:
Aggen DH, Ager CR, Obradovic AZ, Chowdhury N, Ghasemzadeh A, Mao W, Chaimowitz MG, Lopez-Bujanda ZA, Spina CS, Hawley JE, Dallos MC, Zhang C, Wang V, Li H, Guo XV, Drake CG. “Blocking IL1 Beta Promotes Tumor Regression and Remodeling of the Myeloid Compartment in a Renal Cell Carcinoma Model: Multidimensional Analyses” Clin Cancer Res. 2021 Jan 15; 27(2): 608-621.
Spina CS, Tsuruoka C, Mao W, Sunaoshi MM, Chaimowitz M, Shang Y, Welch D, Wang YF, Venturini N, Kakinuma S, Drake CG. “Differential Immune Modulation With Carbon-Ion Versus Photon Therapy” Int J Radiat Oncol Biol Phys. 2021 Mar 1; 109(3): 813-818.
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