CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Tumor-Opsonizing Antibodies Drive Regression of Metastases Only When CD47 Is Disrupted
2.2. Macrophages Infiltrate and Phagocytose CD47-Depleted, IgG-Opsonized B16F10 Nodules
2.3. Tumor Clearance Induced by Opsonization and CD47 Deletion Prolongs Survival, but Some Tumors Escape
2.4. Antibody-Engineered Marrow Macrophages/Monocytes Eliminate Lung Tumor Nodules in WT Metastases, While Anti-Tyrp1 Treatment Alone Does Not
2.5. WT Human Lung Cancer Metastases in Liver Suppressed by Antibody-Engineered Marrow Macrophages/Monocytes
2.6. Antibody-Engineered Marrow Macrophages/Monocytes Are Less Effective When Pre-Loaded with Microparticles
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Quantification of Tumor Burden
4.3. Quantitative Analyses for Estimation of Tumor Growth and Projected Survival
4.4. Marrow Harvest and Engineering
4.5. Cell Culture
4.6. CRISPR-Cas9 Deletion of CD47
4.7. Phagocytosis Assays
4.8. Immunohistochemistry
4.9. Statistical Analyses and Equation Fitting
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Andrechak, J.C.; Dooling, L.J.; Tobin, M.P.; Zhang, W.; Hayes, B.H.; Lee, J.Y.; Jin, X.; Irianto, J.; Discher, D.E. CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies. Cancers 2022, 14, 1930. https://doi.org/10.3390/cancers14081930
Andrechak JC, Dooling LJ, Tobin MP, Zhang W, Hayes BH, Lee JY, Jin X, Irianto J, Discher DE. CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies. Cancers. 2022; 14(8):1930. https://doi.org/10.3390/cancers14081930
Chicago/Turabian StyleAndrechak, Jason C., Lawrence J. Dooling, Michael P. Tobin, William Zhang, Brandon H. Hayes, Justine Y. Lee, Xiaoling Jin, Jerome Irianto, and Dennis E. Discher. 2022. "CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies" Cancers 14, no. 8: 1930. https://doi.org/10.3390/cancers14081930