A DLL3- targeted antibody- drug conjugate eradicates high- grade pulmonary neuroendocrine tumor- initiating cells in vivo. SUPPLEMENTARY MATERIALSwww. DC1. Materials and Methods. Fig. S1. Elevated expression of DLL3 m. RNA in SCLC. Fig. S2. Specificity of anti- DLL3 IHC antibody. Fig. S3. DLL3 protein expression by IHC in representative samples from tissue microarrays.
Fig. S4. In vitro plasma stability of SC1. LD6. 5. Fig. S5. Enumeration of cells with localization of human antibody in the late endosome. Fig. S6. DLL3 knockdown confirmation by flow cytometry. Fig. S7. In vivo efficacy of SC1. LD6. 5, naked SC1.
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· A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Un libro (del latín liber, libri) es una obra impresa, manuscrita o pintada en una serie de hojas de papel, pergamino, vitela u otro material, unidas por un lado (es. Un ebook (scritto anche e-book o eBook), in italiano libro elettronico, è un libro in formato digitale a cui si può avere accesso mediante computer e dispositivi.
D6. 5. Fig. S8. In vivo tolerability of SC1. LD6. 5. Fig. S9. Elimination of TICs by SC1. LD6. 5. Fig. S1. 0.
Off- target toxicities observed in nonhuman primates. Table S1. DLL3 normal tissue expression. Table S2. DLL3 microarray expression in PDX. Table S3. Biacore affinity characterization of SC1. SC1. 6LD6. 5 binding to human, cyno, and rat DLL3.
Table S4. LU6. 4 TIC frequency determination. Table S5. DLL3 whole transcriptome metrics (provided as an Excel file). Author contributions: L. R. S. designed and executed experiments; collected, analyzed, and interpreted data; and wrote the manuscript. A. J. B., W. C. A., M. A. A., and J. H. designed and executed experiments; collected, analyzed, and interpreted data; and reviewed the manuscript.
S. B. and J. L.- M. K. B., R. D., P. A. E., A. L., D. L., M. M., H. S., M. T., S. A. W., and O. F. designed and executed experiments. A. P. and M. A. P. B. S., P. H., J. J., A.
B., P. C., D. H. H., A. D., P. P. M., W. D. T., and M. C. P. coordinated and contributed specimens and molecules critical to this work. J. T. P. and C. M. R. analyzed and interpreted data, including statistical analyses, and contributed to the writing of the manuscript. R. A. S. and S. J. D. designed experiments, analyzed and interpreted data, and wrote the manuscript.
Competing interests: L. R. S., A. J. B., W. C. A., M. A. A., S. B., K. B., R. D., P. A. E., J. H., A. P., A.
L., D. L., J. L.- M., M. M., M. A. P., H. S., M. T., S. A. W., O. F., R. A. S., B. S., and S. J. D. are shareholders in Stemcentrx Inc., a privately held and financed company. The following issued and pending patent applications pertain to the results presented here: U.
S. issued patent: 8,9. U. S. pending patent applications: 1. PCT patent applications: PCT/US1.
PCT/US1. 4//0. 17. Data and materials availability: Materials are available from Stemcentrx under a material transfer agreement.