| First Author | Phinney NZ | Year | 2024 |
| Journal | J Biol Chem | Volume | 300 |
| Issue | 9 | Pages | 107681 |
| PubMed ID | 39159812 | Mgi Jnum | J:354301 |
| Mgi Id | MGI:7732128 | Doi | 10.1016/j.jbc.2024.107681 |
| Citation | Phinney NZ, et al. (2024) Development of betabodies: The next generation of phosphatidylserine targeting agents. J Biol Chem 300(9):107681 |
| abstractText | Externalized phosphatidylserine (PS) is a phospholipid and a selective marker of the tumor microenvironment (TME). It is exposed on the outer leaflet of the plasma membrane of tumor-associated endothelial cells, apoptotic tumor cells, and some viable tumor cells, where it functions in part to suppress immune responses by binding to PS receptors expressed on tumor-infiltrating myeloid cells. PS has been targeted with antibodies, such as bavituximab, that bind the phospholipid via a cofactor, beta2-glycoprotein 1 (beta2GP1); these antibodies showed excellent specificity for tumor vasculature and induce an immune stimulatory environment. We have advanced this concept by developing the next generation of PS targeting agent, a fusion protein (betabody) constructed by linking PS-binding domain V of beta2GP1 to the Fc of an IgG2a. Betabodies bind to externalized PS with high affinity ( approximately 1 nM), without the requirement of a co-factor and localize robustly to the TME. We demonstrate that betabodies are a direct PS-targeting agent that has the potential to be used as anti-tumor therapy, drug delivery vehicles, and tools for imaging the TME. |
