A5114423798- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Sarcoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Complement system in diseases
- Nanoparticle-Based Drug Delivery
Pfizer (United States)
2024
<p>Supplementary Figure 19. Protease activity of select syngeneic and xenograft tumor models was assessed using an activatable cell-penetrating peptide (ACPP)2 bearing the -IPVSLRSG- cleavage sequenced used in Coil-MMP-mIAP301 SGN-CD47M antibodies.</p>
<p>Supplementary Figure 12. Hemagglutination activity of hB6H12.3, SGN-CD47M, MMP-cleaved and an IgG1 isotype control on human red blood cells, as assessed by optical measurement spot size following incubation with increasing concentrations antibodies.</p>
<p>Supplementary Figure 6. hB6H12.3, bearing a human IgG1 Fc region elicits stronger phagocytosis of red blood cells by monocytes in vitro compared to IgG4 competitor antibodies HuF9-G4 and CC-90002.</p>
<p>Supplementary Figure 13. Assessment of the ability hB6H12.3, SGN-CD47M, MMP-cleaved SGN-CD47, and a IgG1 isotype control antibody to induce direct apoptosis THP1 cells, as assessed by flow cytometry Annexin V cell surface expression.</p>
<p>Supplementary Figure 2. Concentration-time profiles of 3H-labeled mIAP301 and Coil-MMP-mIAP301 were profiled in the plasma, liver, tumors BALB/c mice bearing A20 lymphoma once reached approximately 250 mm3 size.</p>
<p>Supplementary Figure 15. Anti-CD47 antibody mediated FcgRIIa-H131 signaling, assessed using FcγRIIa Jurkat NFAT reporter cells incubated with CD47-expressing WIL2-S target and increasing concentrations of anti-CD47 antibodies or isotype control.</p>
<p>Supplementary Figure 17. F4/80 staining of select xenograft tumor models used in the study.</p>
<div>Abstract<p>CD47 is a cell-surface glycoprotein that expressed on normal human tissues and plays key role as marker of self. Tumor cells have co-opted CD47 overexpression to evade immune surveillance, thus blockade highly active area clinical exploration in oncology. However, development CD47-targeted agents has been complicated by its robust expression the toxicities arise from blocking this inhibitory signal. Furthermore, pro-phagocytic signals are not uniformly tumors,...
<p>Supplementary Figure 18. Statistical analysis of tumor growth inhibition from xenograft model experiments shown in 3 the main text.</p>
<p>Supplementary Figure 9. hB6H12.3 induces stronger FcγRIIa-H131 activation than similar anti-CD47 based on the parent mB6H12 murine antibody, as assessed using a Jurkat NFAT reporter assay in presence of WIL2-S target cells that express CD47.</p>
<p>Supplementary Figure 7. hB6H12.3, bearing a human IgG1 Fc region elicits robust antibody-dependent cellular cytotoxicity in the presence of NK cells compared to IgG4 competitor antibodies HuF9-G4 and CC-90002.</p>
<p>Supplementary Figure 5. Anti-CD47 antibody hB6H12.3 is able to kill CD47-expressing cells via caspase-independent apoptosis, as evidence by the upregulation of Annexin V in a dose-dependent manner, assessed flow cytometry on MCF-7 vitro.</p>
<p>Supplementary Figure 16. Production of proteases in culture by cancer cells is sufficient to activate SGN-CD47M restore binding and function.</p>
<p>Supplementary Figure 14. Induction of ADCC, assessed using FcγRIIIa-V158 Jurkat NFAT reporter cells incubated with CD47-expressing WIL2-S target and increasing concentrations anti-CD47 antibodies or isotype control.</p>
<p>Supplementary Figure 4. hBH12.3 inhibits binding of SIRPα to CD47 in a flow cytometry-based assay whereas SGN-CD47M has no effect.</p>
<p>Supplementary Figure 10. Optical assessment was used to characterize the hemagglutination of human RBCs induced by hB6H12.3 and murine antibody mB6H12.</p>
<p>Supplementary Figure 8. hB6H12.3, bearing a human IgG1 Fc region demonstrates enhanced T cell responsiveness compared to IgG4 competitor antibodies HuF9-G4 and CC-90002.</p>
<p>Supplementary Figure 11. Saturation binding analysis of hB6H12.3, SGN-CD47M, and MMP-cleaved SGN-CD47M against recombinant human CD47, as assessed by ELISA.</p>
<p>Supplementary Figure 1. Example mass spectrometry data for MMP2 re-activated masked antibody.</p>