TNFRSF9/4-1BB (Utomilumab Biosimilar) Recombinant Monoclonal Antibody

1. 3 SNPs (rs161827, rs161818, and rs161810) of the CD137 gene and their association with ischemic stroke were studied in a northern Chinese Han population. rs161827 was significantly different between patients with and without diabetes and the controls. rs161818 and rs161810 differed significantly between patients without diabetes and the controls. All 3 were statistically significant in the combination stroke group. PMID: 28755037
2. Herein, we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activates the CD40 and 4-1BB pathways, respectively PMID: 28536305
3. Tonic 4-1BB costimulation in chimeric antigen receptors impedes T cell survival and is vector-dependent. PMID: 28978471
4. Cetuximab-mediated NK-cell expression of CD137 on tumor-infiltrating lymphocytes is dependent on FcgammaRIIIa polymorphism. In neoadjuvant cetuximab-treated patients with head and neck cancer, upregulation of CD137 by intratumoral, cetuximab-activated NK cells correlated with FcgammaRIIIa V/F polymorphism and predicted clinical response. PMID: 27496866
5. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3zeta (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz). PMID: 27530312
6. 4-1BB and 4-1BBL qualify as markers for prediction of patients' course and represent a valuable screening target for patients with acute myeloid leukemia at initial diagnosis. PMID: 27388616
7. the role of CD137-CRDI (cysteine rich domain I) in the binding of CD137-CD137L was further investigated. PMID: 27430526
8. Egr2-driven cell surface proteins LAG-3 and 4-1BB can identify dysfunctional tumor antigen-specific CD8(+) TIL. PMID: 28115575
9. Findings indicate that CD137 antigen is a useful marker that can be used for identifying Mycobacterium tuberculosis (Mtb)-reactive CD4(+) T cells (Mtb-reactive CD4(+) T cells) by flow cytometry. PMID: 28218958
10. Anti-4-1BB single chain variable fragments enhanced surface CD69 expression and interleukin-2 production in stimulated CCRF-CEM cells which confirmed the agonistic effect of the selected single chain variable fragments. The data from this study have provided a rationale for further experiments involving the biological functions of anti-4-1BB single chain variable fragments in future studies. PMID: 28347235
11. Studies suggest that adoptive T cell therapy and CD137 antigen offer much opportunity to raise the efficacy of current cancer immunotherapies. PMID: 26970765
12. in complex with T cell receptor, promotes memory T cells, cell respiration, fatty acid oxidation and mitochondrial biogenesis PMID: 26885860
13. These studies provide the first direct evidence that ligation of tumour necrosis factor superfamily members and their cognate receptors is important for the control of viral lytic replication. PMID: 26467721
14. Our findings provide a novel, TNFRSF9-positive, reactive astrocytic phenotype in human gliomas PMID: 24606203
15. Human genetic evidence for involvement of CD137 in atherosclerosis PMID: 25032953
16. As a result of becoming activated, transferred human T lymphocytes express the inducible surface antigens hPD-1 and hCD137 on their plasma membrane. PMID: 26113085
17. Our results provide biological explanations for the antitumor effects of CD19 CARs and for the observations that CD19 CAR T cells incorporating the 4-1BB costimulatory domain are more persistent than those incorporating CD28 in clinical trials. PMID: 25939063
18. upregulation of CD137 expression through LMP1 by EBV promotes cell survival in T or NK cells PMID: 25409517
19. Based on CD137 or CD154 expression. PMID: 25367298
20. High expression of CD137 is associated with type 1 diabetes. PMID: 24797972
21. DENV C disrupts Daxx and NF-kappaB interaction to induce CD137-mediated apoptosis during DENV infection PMID: 25019989
22. action of agonist anti-4-1BB in suppressing autoimmune and allergic inflammation was completely dependent on Galectin-9 (Gal-9). Gal-9 directly bound to 4-1BB, in a site distinct from the binding site of antibodies and the natural ligand of 4-1BB PMID: 24958847
23. A role for the TNFR-family member CD137 in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of tumor-infiltrating lymphocytes. PMID: 24045181
24. monocytes interact with iNKT cells to increase expression of 4-1BBL and 4-1BB, and in conjunction with this pathway, maintain their numbers at baseline. PMID: 24639347
25. findings show that immunohistochemistry for CD137L is capable of reliably distinguishing small B-cell lymphomas from reactive lymphoid aggregates PMID: 24746207
26. Dengue virus induces CD137 signaling to enhance apoptosis by increasing TNF-alpha production via activation of p38 MAPK. PMID: 23557259
27. this is the first study to indicate that this member of the TNF superfamily, CD137, is modulated by SAHA treatment in breast cancer cells PMID: 22797667
28. The CD137 multi-parameter flow cytometry fast assay allows for phenotypic and functional determination of alloreactive precursor frequencies of both CD4+ and CD8+ T cells with high sensitivity and specificity. PMID: 23750604
29. Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy. PMID: 23560068
30. Taken together, these data provide evidence that the 4-1BB signal is an important regulator of gammadelta T cells PMID: 23640752
31. the mechanisms that account for the effect of CD137 signaling on TNF-alpha production were based on a decrease of TNF-alpha production by antigen presenting cell (APC) and, perhaps, on the increase in APC apoptosis. PMID: 23437083
32. Our results reveal a new regulatory mechanism for CD137L expression that mediates immune escape by HRS cells, and they identify CD137 as a candidate target for immunotherapy of Hodgkin PMID: 23204227
33. Head and neck cancer patients have decreased levels of alternative co-stimulatory receptors OX40 and 4-1BB. PMID: 22204816
34. 4-1BB (CD137), together with CD103, marks mesenteric lymph node dendritic cells (DC) with the highest level of retinal dehydrogenase (RALDH) activity, and ligation of 4-1BB maintains RALDH expression in these gut DC. PMID: 22896640
35. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. PMID: 22901750
36. treatment with CD137 agonistic antibody induces CCL21 expression and DC accumulation close to lymphatic vessels. Collectively, our results demonstrate that the inflammatory function of lymphatic vessels can be regulated by CD137. PMID: 22593548
37. CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis PMID: 21747409
38. significantly positive correlation between CD137 expression and complex coronary stenosis morphology PMID: 21396356
39. Data indicate that 4-1BBL mediates NK-cell immunosubversion in CLL, and thus might contribute to the reportedly compromised efficacy of Rituximab to induce NK-cell reactivity in the disease. PMID: 22144129
40. CD137 activity is directly proportional to colorectal cancer stage. Surgical resection of the tumor results in increased CD134 and CD137 expression PMID: 22343199
41. We show that the inflammatory and cytotoxic function of CD4(+)CD28(null) T cells can be inhibited by blocking OX40 and 4-1BB costimulatory receptors. PMID: 22282196
42. The sCD137 levels correlate with the probability of complications and lethality. The association of sCD137, a product of activated T cells, with the severity of acute pancreatitis suggests that T cells contribute to the pathogenesis of acute pancreatitis. PMID: 21963611
43. CD137 has a role in breast cancer and its specific antibody can be used to enhance trastuzumab efficacy PMID: 22326955
44. conditioned medium from Lewis Lung Carcinoma cells caused significant upregulation of 4-1BB in mast cells PMID: 22343053
45. Data indicate that ex4-1BBL augments 4-1BB expression not only on the primed T cell, but also on DC. PMID: 21745658
46. The measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with diffuse large B-cell lymphoma. PMID: 21670469
47. This work is the first to demonstrate the contribution of CD137 signaling to DENV-mediated apoptosis. PMID: 21669186
48. CD137 ligand can also be expressed as a transmembrane protein on the cell surface and transmit signals into the cells on which it is expressed (reverse signaling). PMID: 20643812
49. Results suggest with a two-step model of M cell differentiation, with initial CD137-independent commitment to the M cell lineage followed by CD137-CD137L interaction of M cells with CD137-activated B cells or dendritic cells for functional maturation. PMID: 20616340
50. Data support a role for CD137 in the recruitment of monocytes to inflammatory tissues. PMID: 20347151

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HGNC: 11924

OMIM: 602250

KEGG: hsa:3604

STRING: 9606.ENSP00000366729

UniGene: Hs.738942