SIRPA (ES-004 Biosimilar) Recombinant Monoclonal Antibody

1. Accumulation of SIRPalpha-inhibited macrophages in tumors favored tumor regression for 1-2 weeks, but donor macrophages quickly differentiated toward non-phagocytic, high-SIRPalpha TAMs. PMID: 28669759
2. SIRP alpha protein is under-expressed in low and high-grades of astrocytoma from patients' brain samples. PMID: 27900675
3. Anti-SIRPA antibody immunotherapy enhances neutrophil and macrophage antitumor activity. PMID: 29158380
4. SIRPalpha might play an important role in the progression of oral leukoplakia and oral cancer, and could be a pivotal therapeutic target in oral squamous cell carcinoma, regulating the phenotype of macrophages via targeting NF-kappaB signaling. PMID: 27793032
5. TTI-621 (SIRPalphaFc) is a fully human recombinant fusion protein that blocks the CD47-SIRPalpha axis by binding to human CD47 and enhancing phagocytosis of malignant cells..These data indicate that TTI-621 is active across a broad range of human tumors. PMID: 27856600
6. data suggest that TTI-621 may be efficacious in triggering the destruction of cancer cells by a diverse population of TAMs found in vivo and support possible combination approaches to augment the activity of CD47 blockade PMID: 29084248
7. CD47, TSP1, and to a lesser extent SIRPalpha facilitate exosome-mediated myeloid-derived suppressor cells chemotaxis and migration. PMID: 27728760
8. exploited by Hepatitis E virus to negative regulated IFN-beta of the host innate immune system to promote viral infection PMID: 26492885
9. Data suggest a reduction in the CD47 antigen/signal-regulatory protein alpha (SIRPalpha) pathway by programmed cell death protein 1 (PD-1) blockade, which regulates Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). PMID: 26573233
10. agents that block the CD47:SIRP-alpha engagement are attractive therapeutic targets as a monotherapy or in combination with additional immune-modulating agents for activating antitumor T cells in vivo PMID: 26116271
11. the data suggest that combinatorial actions of ADAM10 and gamma-secretase on SIRPalpha cleavage promote inflammatory signaling. PMID: 26534964
12. Loss of cell surface CD47 clustering formation and binding avidity to SIRPalpha facilitate apoptotic cell clearance by macrophages. PMID: 26085683
13. Velcro" engineering of high affinity CD47 ectodomain as signal regulatory protein alpha (SIRPalpha) antagonists that enhance antibody-dependent cellular phagocytosis PMID: 25837251
14. negatively regulates neutrophil accumulation during inflammation PMID: 24516072
15. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. PMID: 24968096
16. These results suggest that thrombospondin-1 binding to SIRP-alpha on nonphagocytic cells activates NADPH oxidase, limits vasodilation, and promotes renal ischemia reperfusion injury. PMID: 24511121
17. 'clustering' SIRPalpha into plasma membrane microdomains is essential for activated monocytes and macrophages to effectively interact with CD47 and initiate intracellular signaling PMID: 24143245
18. Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47. PMID: 24550402
19. SIRPA plays a protective role in cardiac hypertrophy through negative regulation of the Toll-like receptor 4/nuclear factor-kappaB pathway. PMID: 24101669
20. These results demonstrate a SIRPalpha-based mechanism that dynamically regulates polymorphonuclear leukocyte inflammatory responses. PMID: 24026300
21. Signal regulatory protein alpha is associated with tumor-polarized macrophages phenotype switch and plays a pivotal role in tumor progression. PMID: 23504854
22. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a(+) cells. PMID: 23669395
23. Expression of SIRPalpha on two low SIRPalpha acute myeloid leukemia (AML) expressing cell lines could be upregulated upon differentiation of the cells. PMID: 23320069
24. SHPS-1 negatively regulates the MyD88-dependent TLR signaling pathway through the inhibition of NF-kappaB activation PMID: 23314616
25. IFN-beta and IFN-gamma/TNF-alpha decrease erythrophagocytosis by human monocytes in vitro, and this effect does not apparently require an increase in SIRP-alpha or SHP-1 expression. PMID: 22738830
26. neutrophils reduce their SIRPalpha expression during apoptosis, which may be part of the functional down-regulation seen in apoptotic neutrophils. PMID: 23271705
27. thymic Sirpalpha(+) cDCs crucially contribute to a process of intrathymic tumor immune tolerance that involves CCR2 and CCL2 PMID: 22815949
28. In the glomeruli of CNS patients carrying mutations in NPHS1, where SD formation is disrupted, the expression of SIRPalpha as well as Neph1 and nephrin was significantly decreased, indicating that SIRPalpha is closely associated with the nephrin complex PMID: 22747997
29. Surfactant protein D (Sp-D) binds to membrane-proximal domain (D3) of signal regulatory protein alpha (SIRPalpha), a site distant from binding domain of CD47, while also binding to analogous region on signal regulatory protein beta (SIRPbeta). PMID: 22511785
30. SIRPalpha1 in hepatic sinusoid Kupffer cells is associated with the extent of autoimmune hepatitis. PMID: 22409853
31. data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor phagocytosis and elimination PMID: 22451913
32. SIRPalpha/CD172a and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen. PMID: 22490440
33. Sensing of cell surface CD47 expression by phagocyte SIRPalpha is a critical determinant of T- and natural killer-cell homeostasis under steady-state conditions in vivo. PMID: 21788504
34. hSIRPa-transgenic Rag2(-/-)gamma(c)(-/-) mice represent a unique mouse strain supporting high levels of human cell engraftment. PMID: 21788509
35. The prolactin receptor (PRLr)-SIRPalpha-integrin complex provides a basis for integrin-PRLr cross-talk that contributes to the biology of breast cancer. PMID: 20826546
36. the relationships between SIRPalpha1 and beta-catenin in leukemia cells. PMID: 21369691
37. Single Nucleotide Polymorphisms in PTPNS1 is associated with inflammatory bowel disease. PMID: 21225905
38. SHP-2 as an essential component of tumor suppression and anoikis mediated by SIRPalpha1 in human breast carcinoma cells as well as in v-Src-transformed cells. PMID: 21169408
39. Poor prognosis of breast cancer patients with high expression of CD47 is due to an active CD47/SIRPA signaling pathway in circulating cells. PMID: 20705613
40. The role of cis dimerization of signal regulatory protein alpha (SIRPalpha) in binding to CD47. PMID: 20826801
41. Findings reveal a novel mechanism for recruitment of PDK1 to the SHPS-1 signaling complex, which is required for IGF-I-stimulated AKT Thr(308) phosphorylation and inhibition of apoptosis. PMID: 20643654
42. Inhibition of engulfment correlates with affinity of CD47 for SIRPA - but only at low levels of CD47. PMID: 20299253
43. SIRPalpha1 specifically affects the SHP-2/FAK/Grb2/Sos-1/MAPK activation loop to downmodulate EGFRvIII-mediated migration and transformation. PMID: 20473329
44. Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells. PMID: 20207740
45. SIRP alpha gene expression is higher in monocytes from autoimmune hemolytic anemia patients, compared with basal expression. PMID: 19874234
46. CD47/SIRP-alpha interactions are implicated in the pathogenesis of DC-driven allergic airway inflammation. PMID: 19748659
47. Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration PMID: 11792697
48. The interaction of SHPS-1 with CD47 may contribute to the recruitment of B lymphocytes via endothelial cells under steady state conditions. PMID: 11907074
49. MyD-1-coupling to this PI 3-kinase-dependent signaling pathway may therefore present a novel target for the development of therapeutic strategies for combating TNFalpha production and consequent inflammatory disease. PMID: 12805067
50. Expression of SIRPalpha1 on astrocytomas may be of considerable importance in brain tumor biology. PMID: 14729615

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HGNC: 9662

OMIM: 602461

KEGG: hsa:140885

STRING: 9606.ENSP00000348307

UniGene: Hs.581021