CDX-585, a Bispecific Antibody with Dual Targeting of ILT4 and PD-1 Checkpoint Pathways
Abstract
:1. Introduction
2. Materials and Methods
2.1. Development and Characterization of Bispecific Antibodies
2.2. Affinity Determination Using Bio-Layer Interferometry
2.3. ELISA Assays
2.4. Flow Cytometry
2.5. Cell-Based PD-1 Signaling Assay
2.6. Immune Cell Activation Assays
2.7. Human T Cell Stimulation
2.8. Mixed Lymphocyte Reaction
2.9. Mouse Xenograft Tumor Model
2.10. Non-Good Laboratory Practice (GLP) Pilot Non-Human Primate Study
2.11. Statistical Analysis
3. Results
3.1. Characterization of Novel ILT4 and PD-1 Antibodies
3.2. Development of the CDX-585 bsAb
3.3. CDX-585 Potently Inhibits PD-1 Signaling and HLA-G Ligand Binding
3.4. CDX-585 Drives M1 Macrophage Polarization
3.5. CDX-585 Enhances Both Myeloid and T Cell Activation
3.6. CDX-585 Enhances T Cell Activation in Mixed Lymphocyte Reactions
3.7. CDX-585 Potentiates CD40-Mediated Immune Cell Activation
3.8. CDX-585 Enhances Antitumor Activity in a SKMEL-5 Mouse Model
3.9. Non-GLP Pilot Study in Non-Human Primates
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Murphy, M.B.; Vitale, L.; Xia, S.; Peng, Z.; O’Neill, T.; Lillquist, J.; Wasiuk, A.; Weidlick, J.; Widger, J.; Mills-Chen, L.; et al. CDX-585, a Bispecific Antibody with Dual Targeting of ILT4 and PD-1 Checkpoint Pathways. Immuno 2023, 3, 273-288. https://doi.org/10.3390/immuno3030018
Murphy MB, Vitale L, Xia S, Peng Z, O’Neill T, Lillquist J, Wasiuk A, Weidlick J, Widger J, Mills-Chen L, et al. CDX-585, a Bispecific Antibody with Dual Targeting of ILT4 and PD-1 Checkpoint Pathways. Immuno. 2023; 3(3):273-288. https://doi.org/10.3390/immuno3030018
Chicago/Turabian StyleMurphy, Michael B., Laura Vitale, Shukai Xia, Zeyu Peng, Thomas O’Neill, Jay Lillquist, Anna Wasiuk, Jeff Weidlick, Jenifer Widger, Laura Mills-Chen, and et al. 2023. "CDX-585, a Bispecific Antibody with Dual Targeting of ILT4 and PD-1 Checkpoint Pathways" Immuno 3, no. 3: 273-288. https://doi.org/10.3390/immuno3030018