BackNon-Fucosylated CD70-directed Antibody
PF-08046040 | SEA-CD70 is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
- PF-08046040; SEA-CD70 is an investigational, humanized, non-fucosylated immunoglobulin G1 monoclonal antibody directed to CD701
- CD70 is a cell-surface ligand of the tumor necrosis factor superfamily, transiently expressed on activated B and T cells and mature dendritic cells2-4 whose receptor, CD27, is widely expressed on B, T, and natural killer cells3,4
- CD70 and CD27 are expressed on AML and MDS malignant blasts as well as on leukemic blasts that propagate the disease.1,5-8
- CD70 has limited expression in normal cells, making it an attractive target in myeloid malignancies2-6
- The non-fucosylated Fc region of PF-08046040; SEA-CD70 has increased affinity for activating FcγRIIIa receptors and minimal affinity for inhibitory FcγRIIb receptors, leading to enhanced Fc-mediated effector function1
Mechanism of Action
PF-08046040 | SEA-CD70 is thought to engage an antitumor immune response through:
- Blockade of CD70/CD27-mediated proliferative signaling in malignant blast cells2
- Antibody-dependent cellular phagocytosis2
- Enhanced antibody-dependent cellular cytotoxicity2
- Complement-dependent cytotoxicity2
Stage of Development
Myeloid Malignancies (R/R AML, MDS)
Phase 1 Monotherapy and Combination