ROCKVILLE, MD, USA I November 14, 2018 I MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced that it had presented a poster titled “Converting PD-L1-induced T-lymphocyte Inhibition into CD137-mediated Co-stimulation via PD-L1 x CD137 Bispecific DART® Molecules”, at the 30th EORTC-NCI-AACR Symposium being held in Dublin, Ireland.
PD-1/PD-L1 blockade is a clinically proven cancer therapeutic strategy that releases an inhibitory brake on T-cell activation. Co-stimulation by CD137, also known as 4-1BB, has been shown to synergistically increase the activity of PD-1/PD-L1 axis blockade. Clinical application of such a combination approach, however, may be limited by toxicity associated with the systemic administration of CD137 agonists. Bispecific antibody targeting strategies afford the feasibility of localizing CD137 co-stimulation to the tumor microenvironment through simultaneous engagement of a tumor-expressed antigen and CD137 expressed on tumor infiltrating lymphocytes. In this poster, MacroGenics demonstrated that bispecific DART or TRIDENT™ proteins constructed using a proprietary PD-L1 blocking monoclonal antibody, or mAb, and a CD137-engaging mAb can further extend immune cell activation observed by concomitant PD-1/PD-L1 axis blockade and CD137 co-stimulation beyond that achieved by the combination of individual mAbs.
The preclinical data presented show that PD-L1 x CD137 bispecific DART and TRIDENT molecules can switch on CD137 co-stimulation strictly in a PD-L1-dependent fashion, limiting the probability of systemic activation where PD-L1 is not expressed. Although tumor adaptive resistance via PD-L1 induction promotes immune escape, PD-L1 x CD137 bispecific molecules can exploit the upregulation of the checkpoint ligand to provide a co-stimulatory signal and further amplify concomitant checkpoint blockade. Additional investigations as a potential therapeutic approach to overcome limitations of existing PD-1/PD-L1-targeting strategies are ongoing.
The poster presented at the 30th EORTC-NCI-AACR Symposium is available for download from the Events & Presentations page on MacroGenics’ website at http://ir.macrogenics.com/events.cfm.
About MacroGenics, Inc.
MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics’ technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company’s website at www.macrogenics.com. MacroGenics, the MacroGenics logo, DART and TRIDENT are trademarks or registered trademarks of MacroGenics, Inc.
SOURCE: MacroGenics
Post Views: 13
ROCKVILLE, MD, USA I November 14, 2018 I MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced that it had presented a poster titled “Converting PD-L1-induced T-lymphocyte Inhibition into CD137-mediated Co-stimulation via PD-L1 x CD137 Bispecific DART® Molecules”, at the 30th EORTC-NCI-AACR Symposium being held in Dublin, Ireland.
PD-1/PD-L1 blockade is a clinically proven cancer therapeutic strategy that releases an inhibitory brake on T-cell activation. Co-stimulation by CD137, also known as 4-1BB, has been shown to synergistically increase the activity of PD-1/PD-L1 axis blockade. Clinical application of such a combination approach, however, may be limited by toxicity associated with the systemic administration of CD137 agonists. Bispecific antibody targeting strategies afford the feasibility of localizing CD137 co-stimulation to the tumor microenvironment through simultaneous engagement of a tumor-expressed antigen and CD137 expressed on tumor infiltrating lymphocytes. In this poster, MacroGenics demonstrated that bispecific DART or TRIDENT™ proteins constructed using a proprietary PD-L1 blocking monoclonal antibody, or mAb, and a CD137-engaging mAb can further extend immune cell activation observed by concomitant PD-1/PD-L1 axis blockade and CD137 co-stimulation beyond that achieved by the combination of individual mAbs.
The preclinical data presented show that PD-L1 x CD137 bispecific DART and TRIDENT molecules can switch on CD137 co-stimulation strictly in a PD-L1-dependent fashion, limiting the probability of systemic activation where PD-L1 is not expressed. Although tumor adaptive resistance via PD-L1 induction promotes immune escape, PD-L1 x CD137 bispecific molecules can exploit the upregulation of the checkpoint ligand to provide a co-stimulatory signal and further amplify concomitant checkpoint blockade. Additional investigations as a potential therapeutic approach to overcome limitations of existing PD-1/PD-L1-targeting strategies are ongoing.
The poster presented at the 30th EORTC-NCI-AACR Symposium is available for download from the Events & Presentations page on MacroGenics’ website at http://ir.macrogenics.com/events.cfm.
About MacroGenics, Inc.
MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics’ technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company’s website at www.macrogenics.com. MacroGenics, the MacroGenics logo, DART and TRIDENT are trademarks or registered trademarks of MacroGenics, Inc.
SOURCE: MacroGenics
Post Views: 13
