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
Xinyue Qi,et al.Nat Commun. 2019.PMCID: PMC6526162
“Costimulation of T cell responses with monoclonal antibody agonists (mAb-AG) targeting 4-1BB showed robust anti-tumor activity in preclinical models, but their clinical development was hampered by low efficacy (Utomilumab) or severe liver toxicity (Urelumab). Here we show that isotype and intrinsic agonistic strength co-determine the efficacy and toxicity of anti-4-1BB mAb-AG. While intrinsically strong agonistic anti-4-1BB can activate 4-1BB in the absence of FcγRs, weak agonistic antibodies rely on FcγRs to activate 4-1BB. All FcγRs can crosslink anti-41BB antibodies to strengthen co-stimulation, but activating FcγR-induced antibody-dependent cell-mediated cytotoxicity compromises anti-tumor immunity by deleting 4-1BB+ cells. This suggests balancing agonistic activity with the strength of FcγR interaction as a strategy to engineer 4-1BB mAb-AG with optimal therapeutic performance. As a proof of this concept, we have developed LVGN6051, a humanized 4-1BB mAb-AG that shows high anti-tumor efficacy in the absence of liver toxicity in a mouse model of cancer immunotherapy.”

2、Intratumoral activation of 41BB co-stimulatory signals enhances CD8 T cell expansion and modulates tumor-infiltrating myeloid cells
Patrick Innamarato,et al.J Immunol. 2021.PMCID: PMC7741883
“The activation of 41BB co-stimulatory signals by agonistic antibodies enhances the expansion and function of tumor-infiltrating lymphocytes (TILs) for treating cancer patients with adoptive cell therapy (ACT). However, the impact of 41BB agonism is not limited to enhancing the activity of T cells and the mechanism by which additional activation of this co-stimulatory axis in tumor-associated myeloid cells is poorly understood. Here, we describe that the intratumoral administration of 41BB agonistic antibodies led to increases in CD8 T cell infiltration followed by tumor regression in murine models. We found that granulocytes and monocytes rapidly replaced macrophages and dendritic cells in tumors following administration of anti-41BB antibodies. Overall, myeloid cells from anti-41BB treated tumors had an improved capacity to stimulate T cells in comparison to control treated tumors. In human co-culture systems, we demonstrated that the agonism of the 41BB-41BBL axis enhanced co-stimulatory signals and effector functions among antigen presenting cells and autologous TILs. Overall, these findings suggest that the effect of 41BB agonistic antibodies are supported by additional co-stimulatory signals from tumor-associated myeloid cells leading to enhanced TIL expansion and function.”

3、TCR-independent CD137 (4–1BB) signaling promotes CD8+-exhausted T cell proliferation and terminal differentiation
Andrea C Pichler,et al.Immunity. 2023.PMCID: PMC10649891
“CD137 (4–1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by CD137 and its role in cancer immune surveillance remain unresolved. Using T cell-specific deletion and agonist antibodies, we found that CD137 modulates tumor infiltration of CD8+-exhausted T (Tex) cells expressing PD1, Lag-3, and Tim-3 inhibitory receptors. T cell-intrinsic, TCR-independent CD137 signaling stimulated the proliferation and the terminal differentiation of Tex precursor cells through a mechanism involving the RelA and cRel canonical NF-κB subunits and Tox-dependent chromatin remodeling. While Tex cell accumulation induced by prophylactic CD137 agonists favored tumor growth, anti-PD1 efficacy was improved with subsequent CD137 stimulation in pre-clinical mouse models. Better understanding of T cell exhaustion has crucial implications for the treatment of cancer and infectious diseases. Our results identify CD137 as a critical regulator of Tex cell expansion and differentiation that holds potential for broad therapeutic applications.”

4、Differentiated agonistic antibody targeting CD137 eradicates large tumors without hepatotoxicity
Ugur Eskiocak,et al.JCI Insight. 2020.PMCID: PMC7141404
“CD137 (4-1BB) is a member of the TNFR superfamily that represents a promising target for cancer immunotherapy. Recent insights into the function of TNFR agonist antibodies implicate epitope, affinity, and IgG subclass as critical features, and these observations help explain the limited activity and toxicity seen with clinically tested CD137 agonists. Here, we describe the preclinical characterization of CTX-471, a fully human IgG4 agonist of CD137 that engages a unique epitope that is shared by human, cynomolgus monkey, and mouse and is associated with a differentiated pharmacology and toxicology profile. In vitro, CTX-471 increased IFN-γ production by human T cells in an Fcγ receptor–dependent (FcγR-dependent) manner, displaying an intermediate level of activity between 2 clinical-stage anti-CD137 antibodies. In mice, CTX-471 exhibited curative monotherapy activity in various syngeneic tumor models and showed a unique ability to cure mice of very large (~500 mm3) tumors compared with validated antibodies against checkpoints and TNFR superfamily members. Extremely high doses of CTX-471 were well tolerated, with no signs of hepatic toxicity. Collectively, these data demonstrate that CTX-471 is a unique CD137 agonist that displays an excellent safety profile and an unprecedented level of monotherapy efficacy against very large tumors.”

5、Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity
Yuan Zhang,et al.Nat Commun. 2018.PMCID: PMC5750237
“Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities.”

6、Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer
Zhiqiang Guo,et al.J Transl Med. 2013.PMCID: PMC3853027
“Background
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. The co-stimulatory receptor CD137 is transiently upregulated on T-cells following activation and increases their proliferation and survival when engaged. Although antagonistic anti-TIM-3 or agonistic anti-CD137 antibodies can promote the rejection of several murine tumors, some poorly immunogenic tumors were refractory to this treatment. 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.
Methods
Mice with established ID8 tumor were intraperitoneally injected with single or combined anti-TIM-3/CD137 monoclonal antibody (mAb); mice survival was recorded, the composition and gene expression of tumor-infiltrating immune cells in these mice was analyzed by flow cytometry and quantitative RT-PCR respectively, and the function of CD8+ cells was evaluated by ELISA and cytotoxicity assay.
Results
Either anti-TIM-3 or CD137 mAb alone, although effective in 3 days established tumor, was unable to prevent tumor progression in mice bearing 10 days established tumor, however, combined anti-TIM-3/CD137 mAb significantly inhibited the growth of these tumors with 60% of mice tumor free 90 days after tumor inoculation. Therapeutic efficacy was associated with a systemic immune response with memory and antigen specificity, required CD4+ cells and CD8+ cells. The 2 mAb combination increased CD4+ and CD8+ cells and decreased immunosuppressive CD4+FoxP3+ regulatory T (Treg) cells and CD11b+Gr-1+ myeloid suppressor cells (MDSC) at tumor sites, giving rise to significantly elevated ratios of CD4+ and CD8+ cells to Treg and MDSC; This is consistent with biasing local immune response towards an immunostimulatory Th1 type and is further supported by quantitative RT-PCR data showing the increased Th1-associated genes by anti-TIM-3/CD137 treatment. The increased CD8+ T cells produced high level of IFN-γ upon tumor antigen stimulation and displayed antigen-specific cytotoxic activity.
Conclusions
To our knowledge, this is the first report investigating the effects of anti-TIM-3/CD137 combined mAb in a murine ovarian cancer model, and our results may aid the design of future trials for ovarian cancer immunotherapy.”

7、Antibody-Targeted TNFRSF Activation for Cancer Immunotherapy: The Role of FcγRIIB Cross-Linking
Luyan Liu,et al.Front Pharmacol. 2022.PMCID: PMC9295861
“Co-stimulation signaling in various types of immune cells modulates immune responses in physiology and disease. Tumor necrosis factor receptor superfamily (TNFRSF) members such as CD40, OX40 and CD137/4-1BB are expressed on myeloid cells and/or lymphocytes, and they regulate antigen presentation and adaptive immune activities. TNFRSF agonistic antibodies have been evaluated extensively in preclinical models, and the robust antitumor immune responses and efficacy have encouraged continued clinical investigations for the last two decades. However, balancing the toxicities and efficacy of TNFRSF agonistic antibodies remains a major challenge in the clinical development. Insights into the co-stimulation signaling biology, antibody structural roles and their functionality in immuno-oncology are guiding new advancement of this field. Leveraging the interactions between antibodies and the inhibitory Fc receptor FcγRIIB to optimize co-stimulation agonistic activities dependent on FcγRIIB cross-linking selectively in tumor microenvironment represents the current frontier, which also includes cross-linking through tumor antigen binding with bispecific antibodies. In this review, we will summarize the immunological roles of TNFRSF members and current clinical studies of TNFRSF agonistic antibodies. We will also cover the contribution of different IgG structure domains to these agonistic activities, with a focus on the role of FcγRIIB in TNFRSF cross-linking and clustering bridged by agonistic antibodies. We will review and discuss several Fc-engineering approaches to optimize Fc binding ability to FcγRIIB in the context of proper Fab and the epitope, including a cross-linking antibody (xLinkAb) model and its application in developing TNFRSF agonistic antibodies with improved efficacy and safety for cancer immunotherapy.”

8、Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression
Jonathan P O Hebb,et al.Cancer Immunol Immunother. 2017.PMCID: PMC7446289
“The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect. The minimal effective dose was 10 μg each. The effect was dependent on CD8 T-cells. Intratumoral administration resulted in superior local and distant tumor control compared to systemic routes, supporting the in situ vaccine concept. In a single tumor A20 model, injection close to the tDLN resulted in similar efficacy as intratumoral and significantly better than targeting a non-tDLN, supporting the role of the tDLN as a viable immunotherapy target in addition to the tumor itself. Distribution studies confirmed expected concentration of antibodies in tumor and tDLN, in keeping with the anti-tumor results. Overall intratumoral or peri-tDLN administration of the novel combination of anti-CTLA4, anti-CD137, and anti-OX40, all agents in the clinic or clinical trials, demonstrates potent systemic anti-tumor effects. This immunotherapeutic combination is promising for future clinical development via both these safe and highly efficacious routes of administration.”

9、Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity
Liming Gui,et al.Cell Rep Med. 2025.PMCID: PMC11866496
“The induction of immunogenic cell death (ICD) impedes tumor progression via both tumor cell-intrinsic and -extrinsic mechanisms, representing a robust therapeutic strategy. However, ICD-targeted therapy remains to be explored and optimized. Through kinome-wide CRISPR-Cas9 screen, NUAK family SNF1-like kinase 1 (NUAK1) is identified as a potential target. The ICD-provoking effect of NUAK1 inhibition depends on the production of reactive oxygen species (ROS), consequent to the downregulation of nuclear factor erythroid 2-related factor 2 (NRF2)-mediated antioxidant gene expression. Moreover, the mevalonate pathway/cholesterol biosynthesis, activated by spliced form of X-box binding protein 1 (XBP1s) downstream of ICD-induced endoplasmic reticulum (ER) stress, functions as a negative feedback mechanism. Targeting the mevalonate pathway with CRISPR knockout or the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor simvastatin amplifies NUAK1 inhibition-mediated ICD and antitumor activity, while cholesterol dampens ROS and ICD, and therefore also dampens tumor suppression. The combination of NUAK1 inhibitor and statin enhances the efficacy of anti-PD-1 therapy. Collectively, our study unveils the promise of blocking the mevalonate-cholesterol pathway in conjunction with ICD-targeted immunotherapy.”

10、Molecular and metabolic pathways mediating curative treatment of a non-Hodgkin B cell lymphoma by Sindbis viral vectors and anti-4-1BB monoclonal antibody
Minjun Yu,et al.J Immunother Cancer. 2019.PMCID: PMC6632218
“Background
Limitations to current therapies for treating non-Hodgkin B cell lymphoma include relapse, toxicity and high cost. Thus, there remains a need for novel therapies. Oncolytic viral (OV) therapy has become a promising cancer immunotherapy because of its potential effectiveness, specificity and long-lasting immunity. We describe and characterize a novel cancer immunotherapy combining Sindbis virus (SV) vectors and the agonistic monoclonal antibody (mAb) to the T cell costimulatory receptor, 4-1BB (CD137).
Methods
A20 lymphoma was transfected with luciferase and tumor cells were inoculated to BALB/c mice. Tumor growth was monitored by IVIS imaging. Tumor bearing mice were treated with Sindbis virus, α4-1BB Ab or SV plus α4-1BB Ab. On day 7 after treatment, splenocytes were harvested and surface markers, cytokines, and transcription factors were measured by flow cytometry or Elispot. Splenic T cells were isolated and RNA transcriptome analysis was performed. Tumor cured mice were rechallenged with tumor for testing immunological memory.
Results
SV vectors in combination with α4-1BB monoclonal antibody (mAb) completely eradicated a B-cell lymphoma in a preclinical mouse model, a result that could not be achieved with either treatment alone. Tumor elimination involves a synergistic effect of the combination that significantly boosts T cell cytotoxicity, IFNγ production, T cell proliferation, migration, and glycolysis. In addition, all mice that survived after treatment developed long lasting antitumor immunity, as shown by the rejection of A20 tumor rechallenge. We identified the molecular pathways, including upregulated cytokines, chemokines and metabolic pathways in T cells that are triggered by the combined therapy and help to achieve a highly effective anti-tumor response.
Conclusions
Our study provides a novel, alternative method for B cell lymphoma treatment and describes a rationale to help translate SV vectors plus agonistic mAb into clinical applications.”

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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