Antibody-Based Platform for Targeted Elimination of Leukemia Cells with Reduced Off-Target Toxicity
These human antibodies target and bind to Siglec-6 for precise immunotherapies treating diseases related to aberrant Siglec-6 expression, such as chronic lymphocytic leukemia (CLL). Chronic lymphocytic leukemia (CLL) is one of the most common adult leukemias, with a lifetime risk of 0.6% for the average American. Current treatment options include monoclonal antibodies and kinase inhibitors. While these therapies extend remissions in most patients, they are not curative. They require continuous use, thereby creating a significant burden; have mechanisms of relapse; and lack specificity for leukemia B cells, perpetuating immune dysfunction in patients. Additionally, most current immunotherapies target broadly expressed B-cell markers, increasing the risk of on-target/off-tumor toxicity and limiting the therapeutic window of dosing.
Allogeneic hematopoietic stem cell transplantation (alloHSCT), a high-risk procedure ruled out for most of the CLL patient population, yields longer remissions or cures in approximately half of patients who have undergone this treatment. While most of alloHSCT-induced graft-versus-leukemia response is T cell-mediated, there is evidence of leukemia-targeting antibodies; key for developing CLL-specific therapies. There is a growing need for therapies that can more precisely distinguish malignant cells from healthy tissue.
Researchers at the University of Florida have identified a set of alloHSCT patient-derived Siglec-6 targeting monoclonal antibodies (mAbs) for selective targeting of disease-associated cells. By focusing on a more restricted surface marker, this approach supports more precise and potentially safer immunotherapy strategies.
Application
Antibody-based therapeutic platform for the treatment of leukemia and other diseases, including fully human monoclonal antibodies, T-cell engaging bispecific antibodies, and antibody-drug conjugates (ADCs) targeting Siglec-6
Advantages
- Targets Siglec-6–expressing cells with high specificity, reducing on-target/off-tumor effects compared to broadly targeted immunotherapies
- Supports multiple therapeutic formats, including bispecific antibodies and ADCs, enabling flexible development across indications
- Enables T-cell recruitment through bispecific T-cell engagers (TCEs), enhancing immune-mediated killing of target cells
- Provides a modular antibody platform adaptable to different disease contexts, expanding potential clinical and commercial applications
Technology
The therapeutic platform consists of engineered antibodies that selectively bind to Siglec-6, a cell surface receptor associated with certain leukemias and immune-related conditions. These antibodies are designed to recognize and attach to target cells with high specificity, enabling more precise identification of diseased cells compared to traditional immunotherapies. In various configurations, the antibodies can be incorporated into therapeutic formats such as TCEs and ADCs. These formats allow the technology to recruit immune cells to attack target cells or deliver therapeutic payloads directly, providing a flexible platform for targeted treatment while minimizing effects on healthy tissue.
Publications
- Cyr et al. (2022), J. Immunother. Cancer 10, e004850
- Nunes et al. (2024), Nat. Commun. 15, 5180
Brochure
