Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Antibodies
2.2. Cell Lines and Reagents
2.3. Mice
2.4. Antibody Binding Assays
2.5. CD47 Competition Assay
2.6. Phagocytosis Assay
2.7. Isolation of HA-Specific TCR CD8+ T Cells
2.8. Cross-Presentation Assay
2.9. In Vivo Efficacy Experiments
2.10. Evaluation of biAb Bioavailability and Binding to RBC
3. Results and Discussion
3.1. Generating Tumor Cells and Anti-CD47/TAA biAbs to Study Tumor-Specific CD47 Targeting In Vitro and In Vivo
3.2. CD47/CD19 biAbs Selectively Target Mouse Lymphoma Cells Expressing Human CD19
3.3. Antitumor Efficacy of CD47-Blocking biAbs
3.4. The Affinity of the Anti-CD47 Arm Is Important for biAb Selectivity and Pharmacological Properties
3.5. CD47/CD19 biAb Induces Adaptive Antitumor Immunity
3.6. CD47/CD19 biAbs Enhance the Therapeutic Effect of Immune Checkpoint Blockade and Chemotherapy
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Dheilly, E.; Majocchi, S.; Moine, V.; Didelot, G.; Broyer, L.; Calloud, S.; Malinge, P.; Chatel, L.; Ferlin, W.G.; Kosco-Vilbois, M.H.; et al. Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity. Antibodies 2018, 7, 3. https://doi.org/10.3390/antib7010003
Dheilly E, Majocchi S, Moine V, Didelot G, Broyer L, Calloud S, Malinge P, Chatel L, Ferlin WG, Kosco-Vilbois MH, et al. Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity. Antibodies. 2018; 7(1):3. https://doi.org/10.3390/antib7010003
Chicago/Turabian StyleDheilly, Elie, Stefano Majocchi, Valéry Moine, Gérard Didelot, Lucile Broyer, Sébastien Calloud, Pauline Malinge, Laurence Chatel, Walter G. Ferlin, Marie H. Kosco-Vilbois, and et al. 2018. "Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity" Antibodies 7, no. 1: 3. https://doi.org/10.3390/antib7010003