University of Pittsburgh researchers have identified a fully human antibody targeting ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) with the potential to treat a variety of cancers.
Description
ENPP1 is a type II transmembrane glycoprotein. It plays an important role in immunological responses to various stimuli and regulates immune cells such as neutrophils, Blymphocytes and natural killer (NK) cells. ENPP1 expression in M2 macrophages is heightened in the presence of cancer and linked to tumor growth promotion and spread. The use of antibodies specifically targeting ENPP1 could stimulate an immune response causing immunosuppression in the tumor leading to cell death. This novel approach has the potential to target many cancers with a view to improving patient outcomes and mortality.
Applications
1, Breast cancer
2. Lung cancer
3. Ewing sarcoma
Advantages
In recent years, immunotherapy has been a promising area of interest in the treatment of cancer. Immunotherapy can be specifically tailored to individual patients resulting in more targeted therapy and less adverse events normally associated with systemic therapies like radiotherapy and chemotherapy.
Previous inhibitors of ENPP1 have been found to have poor bioavailability and some have shown hyperactivation of the immune responses. These first fully human antibodies are designed to specifically target ENPP1. They have a high level of specificity reducing the risk of off-target side effects, and due to being fully human, reduces the risk of immunogenicity seen with non-human antibodies.
Invention Readiness
In vitro testing has shown these novel antibodies target different epitopes on ENPP1 and can induce cell death. These antibodies can also be used with ADC, BiTE, BiKE and CAR-T technology. Two fully human antibodies, 17-Fab and 3G12-Fab have been discovered. These antibodies showed nano-molar levels of affinity to ENPP1 and specific binding to ENPP1 expressing Hep G2 cancer cells. They do not compete, and both bind to very different epitopes on ENPP1. Combining these antibodies with bispecific T cell engager (BiTE) technology induced T cell mediated cytotoxicity in ENPP1 positive cells. Likewise, these antibodies can be incorporated with CAR-T cell therapy and could also be used in conjunction with bispecific killer cell engagers (BiKE) and antibody-drug conjugates (ADC), to specifically target cells overexpressing ENPP1 and induce cell death.
IP Status
https://patents.google.com/patent/WO2023250122A1
