SUMMARY
The problem: Chronic, non‐healing wounds have reached epidemic proportions and have a sustainable impact on both an individual’s quality of life and on healthcare costs as a whole
- The field of wound healing is of critical importance in medicine, addressing the urgent need for effective treatments for chronic, non-healing wounds. These wounds, which can result from conditions such as diabetes or radiation therapy, significantly affect patients' quality of life and represent a substantial burden on healthcare systems.
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Wound healing involves a complex, well-orchestrated process through four main phases: hemostasis, inflammation, proliferation, and remodeling. Each phase relies on the precise signaling of chemokines and cytokines to ensure proper cellular responses and tissue regeneration. In particular, dendritic cells (DCs) play an essential role in maintaining immune homeostasis and facilitating wound repair by clearing cellular debris through a process known as efferocytosis. However, chronic wounds often exhibit dysregulated signaling that impairs the healing process, necessitating new approaches to enhance wound recovery.
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Current approaches to treating chronic, non-healing wounds often fall short due to incomplete understanding and management of the underlying dysfunctional immune responses. For example, diabetic wounds frequently suffer from poorly regulated inflammation, leading to non-productive immune responses and stalled healing, eventually resulting in severe complications like limb amputation. Additionally, radiation-induced oral mucositis (RIOM), caused by cancer treatments, creates lesions in the oral cavity that are difficult to heal because radiation disrupts the normal wound-healing cascade and kills immune cells crucial for debris clearance. Existing therapies primarily focus on cancer treatment, not addressing the need for wound healing in these contexts. As a result, there is a significant unmet clinical need for innovative solutions that can effectively harness the immune system to promote wound repair in these challenging scenarios.
The proposed solution: Engineered Flt3L to promote wound healing, specifically targeting non-healing wounds like diabetic ulcers and radiation-induced oral mucositis. Flt3L stimulates hematopoietic progenitors, enhancing the differentiation of classical dendritic cells, which play a crucial role in immune regulation and tissue repair.
- Flt3L is a protein that acts on hematopoietic progenitors and is essential for the differentiation of classical dendritic cells. Flt3L is currently used as a therapeutic agent primarily for immuno-therapeutic cancer treatments in proinflammatory settings. The faculty inventor, Jeffrey Hubbell, offers a novel application of FLt3L in the context of facilitating the healing of non-healing wounds. The approach capitalizes on the protein's role in expanding the dendritic cell compartment, pivotal in resolving chronic inflammation and promoting tissue regeneration.
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Dr. Hubbell developed an engineered version of the Flt3L and has conducted studies to treat mouse models exhibiting non-healing wounds, including a Type 2 diabetic excisional wound model and a radiation-induced oral mucositis (RIOM) model. The administration of Flt3L enhances dendritic cell frequency in wound tissues, which subsequently improves wound healing. Furthermore, the engineered version of Flt3L, which significantly reduces the therapeutic dose required by 20-fold, represents a substantial improvement over current treatments, making this technology not only innovative but potentially transformative for patients suffering from chronic wounds.
ADVANTAGES
ADVANTAGES
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Enhances wound healing through increased frequency of dendritic cells in wound tissue
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Allows uninterrupted cancer treatment by reducing lesions caused by radiation-induced oral mucositis
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Promotes systemic healing through clearance of cellular debris and non-productive inflammation control
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Enhanced efficiency with novel engineering reducing necessary dosage 20-fold
APPLICATIONS
June 2, 2024
Proof of concept
Patent Pending
Licensing,Co-development
Jeffrey Hubbell