Catalog No.	PA007275.r1
Product Name	Anti-mouse CD137 (TNFRSF9 or 4-1BB) Antibody (Clone: LOB12.3) | PA007275.r1
Supplier Name	Syd Labs, Inc.
Brand Name	Syd Labs
Synonyms	cluster of differentiation 137, CD137, TNFRSF9
Summary	The anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: LOB12.3) was produced in mammalian cells.
Clone	LOB12.3
Isotype	Rat IgG1 Kappa
Specificity/Sensitivity	The in vivo grade recombinant anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: LOB12.3) specifically binds to the mouse 4-1BB protein.
Applications	ELISA, flow cytometry, neutralization, functional assays such as bioanalytical PK and ADA assays, and those assays for studying biological pathways affected by the mouse 4-1BB protein.
Form Of Antibody	0.2 uM filtered solution, pH 7.4, no stabilizers or preservatives.
Endotoxin	< 1 EU per 1 mg of the protein by the LAL method.
Purity	>95% by SDS-PAGE under reducing conditions and HPLC.
Shipping	The in vivo grade recombinant anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: LOB12.3) is shipped with ice pack. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage	Use a manual defrost freezer and avoid repeated freeze-thaw cycles. 12 months from date of receipt, -20 to -70°C as supplied. 1 month from date of receipt, 2 to 8°C as supplied.
Note	Recombinant rat IgG1 isotype control antibody and Recombinant human IgG1 isotype control antibodies are available. Condition of sample preparation and optimal sample dilution should be determined experimentally by the investigator.
Order Offline	Phone: 1-617-401-8149 Fax: 1-617-606-5022 Email: message@sydlabs.com Or leave a message with a formal purchase order (PO) Or credit card.

Description

PA007275.r1: Recombinant Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody(Clone: LOB12.3), Rat IgG1 Kappa

The anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: LOB12.3) was produced in mammalian cells.

Background of Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody (Clone: LOB12.3)

The LOB12.3 antibody binds to 4-1BB (TNFRSF9 or CD137), one representative TNF receptor family co-stimulatory receptor. The 4-1BB protein is expressed on a wide variety of cell types, including activated T cells, NK cells, DCs, B cells, monocytes, and neutrophils. Anti-4-1BB-induced CD8+ T responses play a dominant role in anti-tumor immunity, such as induction of more effector molecules released from CD8+ T cells, increased proliferation and decreased apoptosis of CD8+ T cells.

References for Anti-mouse CD137 (TNFRSF9 or 4-1BB) Antibody(LOB12.3):

1、Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity
Qi, X., et al. Nat Commun. 2019 May 20;10(1):2141. doi: 10.1038/s41467-019-10088-1. PMID: 31105267
“To generate anti-human 4-1BB antibody LYGN6051, Balb/C and SJL mice were immunized with human 4-1BB protein and pcDNA3.1-human CD137 plasmid. …Both LOB12.3 and 3H3 Abs showed anti-tumor efficacy (Fig. 1a, b) but they exhibited distinct liver toxicity profiles; 3H3 significantly increased alanine transaminase (ALT) levels, whereas LOB12.3 had minimal impact on ALT levels (Fig. 1c, d). …Using an in vitro co-stimulation assay, we found LOB12.3 and 3H3 had a comparable ability to activate T cells in total splenocyte preparations. …Standard hybridoma method was used to obtain monoclonal Abs against human 4-1BB using the splenocytes of the immunized mice. …The clone 605 with FcγRIIB-dependent agonistic activity was selected for further engineering.”

2、Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine
Bartkowiak, T., et al. Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):E5290-9. doi: 10.1073/pnas.1514418112. PMID: 26351680
“Our preclinical findings from both s.c. and vaginally implanted HPV+ tumors suggest that the efficacy of these ongoing clinical studies could be profoundly enhanced through combination with 4-1BB (CD137) agonist antibodies. …Beyond the impact on cervical cancer and other HPV-driven malignancies, these data may also provide insight for designing effective combination vaccine and checkpoint blockade trials for non-HPV cancers. …Previously, we identified 15–19 amino acid peptides derived from HPV-16 E6 and E7, which were the target of measurable T-cell responses in 19/22 patients who remained recurrence-free following treatment for high grade cervical intraepithelial neoplasia (CIN) versus in 0/10 patients who relapsed. …HPV E6/E7-driven TC-1 tumors are an established murine model of cervical cancer. …Significant therapeutic responses, however, were observed when checkpoint modulating antibodies were administered in combination with the HPV peptide vaccine.”

3、Curing mice with large tumors by locally delivering combinations of immunomodulatory antibodies
Dai, M., et al. Clin Cancer Res. 2015 Mar 1;21(5):1127-38. doi: 10.1158/1078-0432.CCR-14-1339. PMID: 25142145
“A four-mAb combination (anti-CD137/PD-1/CTLA-4/CD19) was most efficacious, particularly against large tumors. …Our findings support the hypotheses by demonstrating frequent CR and long-term survival in all of three mouse tumor models (SW1 and B16 melanoma, TC1 lung carcinoma) and show that injection of tumors is therapeutically more efficacious than systemic administration to induce a strong local and systemic response. …Encouraged by clinical responses with mAb combinations we feel that the four-mAb combination should be evaluated in humans. …To obtain normal cells (presumably fibroblasts) to compare the immunologic effect with that of transplanted tumor cells, one female mouse, syngeneic to the tumor being studied in parallel, was euthanized after which the lungs removed, cut into approximately 1-mm pieces, which were incubated in IMEM medium with 500 μg/mL liberase at 37°C for 1 hour. …Single-cell suspensions from spleens and lymph nodes were prepared as published.”

4、Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice
Murphy, J. T., et al. Blood. 2014 Apr 3;123(14):2172-80. doi: 10.1182/blood-2013-12-544742. PMID: 24558202
“DTA-1 (anti-GITR), OX86 (anti-OX40), FGK45.5 (anti-CD40), GK1.5 (anti-CD4), 11B11 (anti-IL-4), and TA99 (anti-Tyrp-1) were produced and purified by the Monoclonal Antibody Core Facility at MSKCC. LOB12.3 (anti-4-1BB), 1A8 (anti-Ly6G), LTF-2 (rat immunoglobulin G2b [IgG2b] isotype control), and HRPN (rat IgG1 isotype control) were purchased from Bio X Cell. …Murinized DTA-1 (mDTA-1) was obtained from Merck Research Laboratories. Ba103 (anti-CD200R3) was purchased from Hycult Biotech. …All reagents were purchased from Thermo Scientific unless otherwise stated. …Mice were treated with DTA-1 or LTF-2 on days −11 and −7 relative to sera collection. …Statistical differences between experimental groups were determined by using the unpaired 2-tailed Student t test and GraphPad Prism software.”

5、Localized immunotherapy via liposome-anchored Anti-CD137 + IL-2 prevents lethal toxicity and elicits local and systemic antitumor immunity
Kwong, B., et al. Cancer Res. 2013 Mar 1;73(5):1547-58. doi: 10.1158/0008-5472.CAN-12-3343. PMID: 23436794
“Using the murine B16F10 model, we show here that local therapy with anti-CD137 liposomes and IL-2 liposomes leads to potent antitumor activity with no evidence for systemic toxicity, unlike i.t. soluble anti-CD137 + IL-2 treatment. …Thus, liposomal delivery enables aggressive local treatment with high doses of immunotherapeutic agents, promoting a systemic immune response without systemic toxicity. …We next tested whether the dramatic reduction in systemic exposure achieved by liposome-anchored delivery impacted the systemic toxicity of αCD137 + IL-2Fc therapy. …Immunoliposomes also bound to 5% to 15% of CD8+ T cells in the proximal TDLNs but were not detectable in spleens or distal lymph nodes following intratumoral injections (Fig. 2F), confirming that lymphatic drainage of liposomes was confined to the treatment-proximal lymph node. …Importantly, no symptoms of inflammatory toxicity were detected during the sustained schedule of immunotherapy, indicating that localized immunoliposome treatment allows for a broad therapeutic window.”

6、Long-lasting complete regression of established mouse tumors by counteracting Th2 inflammation
Dai, M., et al. J Immunother. 2013 May;36(4):248-57. doi: 10.1097/CJI.0b013e3182943549. PMID: 23603859
“Mice with intraperitoneal ID8 ovarian carcinoma or subcutaneous SW1 melanoma were injected with monoclonal antibodies (mAbs) to CD137+PD-1+CTLA4 7–15 days after tumor initiation. …Survival of mice with ID8 tumors tripled and >40% of mice with SW1 tumors remained healthy >150 days after last treatment and are probably cured. …This is consistent with shifting the tumor microenvironment from an immunosuppressive Th2 to an immunostimulatory Th1 type and is further supported by PCR data. …Adding an anti-CD19 mAb to the 3 mAb combination in the SW1 model further increased therapeutic efficacy. …Data from ongoing experiments show that intratumoral injection of a combination of mAbs to CD137+PD-1+CTLA4+CD19 can induce complete regression and dramatically prolong survival also in the TC1 carcinoma and B16 melanoma models, suggesting that the approach has general validity.”

7、Combinatorial PD-1 blockade and CD137 activation has therapeutic efficacy in murine cancer models and synergizes with cisplatin
Wei, H., et al. PLoS One. 2013 Dec 19;8(12):e84927. doi: 10.1371/journal.pone.0084927. PMID: 24367702
“In spite of the promising antitumor efficacy of several mAbs, many tumors are refractory to treatment with single anti-CD137, anti-PD-1 or anti-CTLA4 mAbs [25,26] and combinations of two or more mAbs may be needed. …For experiments conducted in China, 6 to 8 -week female C57BL were purchased from the Animal Experimental Center of the Second Military Medical University and animal protocols were approved by the Institutional Review Board of Second Military Medical University. …We next repeated the above experiments by using two different clones of mAb against CD137 (2A and lob12.3). …Notably, we did not detect any expression of CD137 and PD-1 molecules and their respective ligands CD137L and PD-L1/PD-L2 on the surface of ID8 ovarian cancer cells (data not shown), excluding the possibility that inhibition of ID8 tumor growth in vivo is directly mediated by the anti-CD137 plus anti-PD-1 mAbs. …While administration of anti-CD137 mAb as a single agent similarly increases CD8+ T cells, these have no functional activity, which may be attributed to up-regulation of co-inhibitory PD-1 and TIM-3 molecules induced by CD137.”

8、Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer
Guo, Z., et al. J Transl Med. 2013 Sep 17;11:215. doi: 10.1186/1479-5876-11-215. PMID: 24044888
“We tested the antitumor efficacy, defined as prolonged overall survival, of single or combined anti-TIM-3 and anti-CD137 mAb in C57BL/6 mice transplanted i.p. 3 or 10 days previously with 1 × 106 ID8 cells. …We did not detect any expression of TIM-3 and CD137 molecules and their respective ligands Galectin-9 and CD137L on the surface of ID8 ovarian cancer cells (data not shown), excluding the possibility that inhibition of ID8 tumor growth in vivo is directly mediated by anti-TIM-3 or anti-CD137 mAb. …To understand the apparent synergy between TIM-3 blockade and CD137 activation in the ID8 tumor model, we sought to dissect the effects of single or combined mAb on tumor-infiltrating immune cells (TIIC) in peritoneal lavage. …T-cell immunoglobulin and mucin domain 3 (TIM-3) is known as a negative immune regulator and emerging data have implicated TIM-3 a pivotal role in suppressing antitumor immunity. …In this study, we sought to evaluate whether combined TIM-3 blockade and CD137 activation would significantly improve the immunotherapy in the murine ID8 ovarian cancer model.”

9、CD4+ T cells develop antiretroviral cytotoxic activity in the absence of regulatory T cells and CD8+ T cells
Manzke, N., et al. J Virol. 2013 Jun;87(11):6306-13. doi: 10.1128/JVI.00432-13. PMID: 23536666
“Costimulatory receptors such as CD134 and CD137 (54) induce this transcription factor after binding of their ligands. …To characterize the role of the costimulatory receptor CD137, infected mice were treated with 100 μg of anti-CD137 (clone LOB12.3; Bioxcell) administered every other day from day four after FV infection by i.p. injection. …As shown previously, CD8+ T cell depletion resulted in significantly increased viral loads, whereas Treg depletion produced significant reductions in viral loads due to enhanced CD8+ T cell responses. …This control over viral loads was lost when CD4+ T cells were also depleted in addition to CD8+ T cells and Tregs. …In HIV-infected patients, CD4+ T cells that could kill HIV-infected target cells in vitro were found.”

10、Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production
Curran, M. A., et al. PLoS One. 2011 Apr 29;6(4):e19499. doi: 10.1371/journal.pone.0019499. PMID: 21559358
“4-1BB (CD137) belongs to the Tumor Necrosis Factor Receptor (TNFR) superfamily and is transiently upregulated on both CD4+ and CD8+ T-cells following activation. …Prior studies have shown that agonistic 4-1BB antibodies with or without CTLA-4 blockade can promote the rejection of some murine tumors and ameliorate auto-immune toxicity; however, poorly immunogenic tumors such as B16 melanoma do not respond to antibody therapy alone. …We found that α4-1BB and αCTLA-4 synergized in rejecting pre-implanted B16 melanomas in conjunction with a B16-Flt3-ligand (FVAX) but not a B16-GMCSF (GVAX) vaccine. …By combining T-cell co-inhibitory blockade with co-stimulatory activation, we were able to induce rejection of poorly immunogenic B16 melanoma tumors. …To understand the apparent synergy between CTLA-4 blockade and 4-1BB activation in the context of our Flt3-ligand base vaccine, we sought to dissect the effects of each therapy on T-cell infiltration of tumor in this background.”

Related Recombinant IgG Reference Antibodies:

Recombinant rat lgG1 isotype control antibody
Recombinant human IgG1 isotype control antibodies

Syd Labs provides the following anti-mouse 4-1BB antibodies:

Anti-mouse 4-1BB monoclonal antibody (Clone: 3H3)

Anti-mouse CD137 Antibody (LOB12.3) from: Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody(Clone: LOB12.3): PA007275.r1 Syd Labs

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