These newly identified cells can be generated outside the body and then infused along with anti-tumor antibodies like cetuximab or rituxan.
Monoclonal antibodies are a potentially specific and non-toxic way to treat tumors. The primary way in which most anti-cancer antibodies work is by coating tumor cells which then signal specific types of white blood cells to recognize the tumor as foreign and kill it (a process called antibody-dependent cellular cytotoxicity or, ADCC). Although some antibody therapies have achieved success in cancer therapy (for example, rituxan, herceptin, and cetuximab), activity is often suboptimal and finding effective antibodies has been difficult. The identification and administration of efficient effector subsets responsible for mediating sufficient ADCC in humans could lead to the development of more synergistic and combination therapies that would enhance the effect of therapeutic Abs.
University of Pennsylvania researchers have identified a new type of white blood cells (called hybrid neutrophils) that have anti-tumor effects and can markedly augment ADCC to increase tumor killing. These cells can also support the other arm of the immune system, T cells, which also kill tumor cells. The researchers have also developed methods of extracting immature granulocytes from bone marrow and blood, differentiating and expanding them into hybrid neutrophils, which could then be infused back into the donors, alone or along with anti-tumor antibodies.
The administration of antibodies against tumor (or possibly even pathogen-specific antigens) in combination with hybrid neutrophils could represent an effective strategy to inhibit tumor growth or infectious processes. Finding ways to enhance the suboptimal ADCC process would have major implications for a wide variety of antibody therapeutics.
- Hybrid neutrophils are able to mediate efficient ADCC compared to canonical neutrophils
- Hybrid neutrophils can be generated from bone marrow or G-CSF/GMCSF mobilized peripheral blood in large numbers
- It may be possible to induce these cells within the body by specific drugs
- The most potent receptors for triggering ADCC are highly up-regulated on hybrid neutrophils
- Hybrid neutrophils exhibit a prolonged survival time compare to canonical neutrophils
- This platform would be applicable to virtually any existing or newly developed anti-tumor antibody
- Cancer immunotherapy
- Infectious diseases
Stage of Development:
- In vitro experiments have been performed with future in-vivo experiments planned.
- Hybrid neutrophils can routinely be generated from bone marrow or peripheral blood immature granulocytes.
- Demonstrated clinical potential of hybrid cells to mediate ADCC in vivo using mouse tumor models
- Identified mechanisms of hybrid neutrophil cytotoxicity triggered by tumor Ag specific Abs.
US Patent Pending (15/756,473)
Docket # 15-7586