Catalog No.	PA007276.r2a
Product Name	Anti-mouse CD137 (TNFRSF9 or 4-1BB) Antibody (Clone: 3H3) | PA007276.r2a
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: 3H3) was produced in mammalian cells.
Clone	3H3
Isotype	Rat IgG2a Kappa
Specificity/Sensitivity	The in vivo grade recombinant anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: 3H3) 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.
Shipping	The in vivo grade recombinant anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: 3H3) 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 IgG2a 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

PA007276.r2a: Recombinant Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody (Clone: 3H3), Rat IgG2a Kappa

The anti-mouse 4-1BB monoclonal antibody (clone: 3H3) was produced in mammalian cells.

Background of Anti-mouse 4-1BB Monoclonal Antibody (Clone: 3H3)

The 3H3 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 4-1BB(CD137) Antibody(3H3):

1、34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2
et al.J Immunother Cancer. 2019.PMCID: PMC6833180
“Background
Cancer cells require outside supply of some non-essential amino acids (NEAAs) to survive. Dietary deprivation of select (NEAAs) can slow down the growth of multiple solid tumors in mice, creating a new non-drug strategy in cancer treatment. However, deprivation of NEAAs could negatively impact the immune activation, an essential process for immunotherapy, because fast cell proliferation poses a higher demand for building blocks such as NEAAs. It is not clear whether dietary NEAA deprivation could be combined with immunotherapy for better safety-efficacy profiles.
Methods
In this study, we tested the effects of NEAA-deprived diets and checkpoint inhibitor anti-PD-1 and anti-PD-L1 in colon cancer using syngeneic mouse model (Balb/c) bearing tumors of mouse colorectal cancer cell line CT-26. Three diets were tested, including a natural rodent diet Teklad ENVIGO Global 16% Protein Rodent Diet (control 1), a formulated NEAA-complete diet COMPLETE (control 2, using amino acid mix in place of protein), and a formulated NEAA-deprived diet FTN203 (treatment, using amino acid mix in place of protein). Both COMPLETE and FTN203 have the same nutritional structures, contain 17% w/w protein equivalent, and are isocaloric. After tumor size-based randomization, these diets were provided to mice ad libitum throughout the whole test. Each of these diets was used alone or combined with anti-PD-1 antibody (i.p., twice per week for 2 weeks) or anti-PD-L1 antibody (i.v., twice per week for 2 weeks).
Results
We found 1) On day 24 post tumor implantation, NEAA-deprived diet FTN203 significantly reduced tumor growth when used alone, compared to the group fed with Teklad ENVIGO (by 81%, P=0.0054, unpaired t-test after Welch correction) and COMPLETE (by 81%, P=0.013), respectively; 2) The efficacy of FTN203 is comparable with that of anti-PD-1 or anti-PD-L1 in tumor growth and median survival; 3) FTN203 did not negate the efficacy of anti-PD-1 or anti-PD-L1 immunotherapy antibody when combined; 4) FTN203 significantly improved the efficacy of anti-PD-1 by further reducing the tumor growth (by 80% on day 26, P=0.046) and increasing the median survival (by 5 days or 14%, Log-rank test P= 0.031), against the combo of COMPLETE and anti-PD-1; 5) None of the mono or combo treatments caused body weight loss.”

2、Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors
Tyrel T Smith,et al.J Clin Invest. 2017.PMCID: PMC5451231
“Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.”

3、4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers
Karolina I Woroniecka,et al.Clin Cancer Res. 2020.PMCID: PMC7073290
“Purpose:
The success of checkpoint blockade against glioblastoma (GBM) has been disappointing. Anti-PD-1 strategies may be hampered by severe T-cell exhaustion. We sought to develop a strategy that might license new efficacy for checkpoint blockade in GBM.
Experimental Design:
We characterized 4-1BB expression in tumor infiltrating lymphocytes (TIL) from human GBM. We implanted murine tumor models including glioma (CT2A), melanoma (B16), breast (E0771), and lung carcinomas (LLC) intracranially (IC) and subcutaneously (SC), characterized 4-1BB expression, and tested checkpoint blockade strategies in vivo.
Results:
Our data reveal that 4-1BB is frequently present on non-exhausted CD8+ tumor-infiltrating lymphocytes (TIL) in human and murine GBM. In murine gliomas, 4-1BB agonism and PD-1 blockade demonstrate a synergistic survival benefit in a CD8+ T-cell dependent manner. The combination decreases TIL exhaustion and improves TIL functionality. This strategy proves most successful against intracranial (IC) CT2A gliomas. Efficacy in all instances correlates with the levels of 4-1BB expression on CD8+ TIL, rather than with histology or with IC versus SC tumor location. Proffering 4-1BB expression to T-cells licenses combination 4-1BB agonism and PD-1 blockade in models where TIL 4-1BB levels had previously been low and the treatment ineffective.
Conclusion:
While poor T-cell activation and severe T-cell exhaustion appear to be limiting factors for checkpoint blockade in GBM, 4-1BB agonism obviates these limitations and produces long-term survival when combined with anti-PD-1 therapy. Furthermore, this combination therapy is limited by TIL 4-1BB expression, but not by the intracranial compartment, and therefore may be particularly well-suited to GBM”

4、Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy
Kin Man Au,et al.Sci Adv. 2020.PMCID: PMC7455497
“Activation of the innate immune system and natural killer (NK) cells has been a key effort in cancer immunotherapy research. Here, we report a nanoparticle-based trispecific NK cell engager (nano-TriNKE) platform that can target epidermal growth factor receptor (EGFR)–overexpressing tumors and promote the recruitment and activation of NK cells to eradicate these cancer cells. Moreover, the nanoengagers can deliver cytotoxic chemotherapeutics to further improve their therapeutic efficacy. We have demonstrated that effective NK cell activation can be achieved by the spatiotemporal coactivation of CD16 and 4-1BB stimulatory molecules on NK cells with nanoengagers, and the nanoengagers are more effective than free antibodies. We also show that biological targeting, either through radiotherapy or EGFR, is critical to the therapeutic effects of nanoengagers. Last, EGFR-targeted nanoengagers can augment both NK-activating agents and chemotherapy (epirubicin) as highly effective anticancer agents, providing robust chemoimmunotherapy.”

5、T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity
Marta Canel,et al.eLife. 2020.PMCID: PMC6974352
“Focal Adhesion Kinase (FAK) inhibitors are currently undergoing clinical testing in combination with anti-PD-1 immune checkpoint inhibitors. However, which patients are most likely to benefit from FAK inhibitors, and what the optimal FAK/immunotherapy combinations are, is currently unknown. We identify that cancer cell expression of the T-cell co-stimulatory ligand CD80 sensitizes murine tumors to a FAK inhibitor and show that CD80 is expressed by human cancer cells originating from both solid epithelial cancers and some hematological malignancies in which FAK inhibitors have not been tested clinically. In the absence of CD80, we identify that targeting alternative T-cell co-stimulatory receptors, in particular OX-40 and 4-1BB in combination with FAK, can drive enhanced anti-tumor immunity and even complete regression of murine tumors. Our findings provide rationale supporting the clinical development of FAK inhibitors in combination with patient selection based on cancer cell CD80 expression, and alternatively with therapies targeting T-cell co-stimulatory pathways.”

6、Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells
Nicholas M Adams,et al.bioRxiv. 2024.PMCID: PMC11430140
“The cohesin protein complex extrudes chromatin loops, stopping at CTCF-bound sites, to organize chromosomes into topologically associated domains, yet the biological implications of this process are poorly understood. We show that cohesin is required for the post-mitotic differentiation and function of antigen-presenting dendritic cells (DCs), particularly for antigen cross-presentation and IL-12 secretion by type 1 conventional DCs (cDC1s) in vivo. The chromatin organization of DCs was shaped by cohesin and the DC-specifying transcription factor IRF8, which controlled chromatin looping and chromosome compartmentalization, respectively. Notably, optimal expression of IRF8 itself required CTCF/cohesin-binding sites demarcating the Irf8 gene. During DC activation, cohesin was required for the induction of a subset of genes with distal enhancers. Accordingly, the deletion of CTCF sites flanking the Il12b gene reduced IL-12 production by cDC1s. Our data reveal an essential role of cohesin-mediated chromatin regulation in cell differentiation and function in vivo, and its bi-directional crosstalk with lineage-specifying transcriptionfactors.”

7、Elimination of acquired resistance to PD-1 blockade via the concurrent depletion of tumour cells and immunosuppressive cells
Gang Xue,et al.Nat Biomed Eng. 2022.PMCID: PMC8595849
“Antigen release resulting from the death of tumour cells induced by chemotherapies and targeted therapies can augment the antitumor responses induced by immune checkpoint blockade (ICB). However, tumours responding to ICB therapies often become resistant to them. Here, we show that the specific targeting of tumour cells promotes the growth of tumour-cell variants that are resistant to ICB, and that the acquired resistance can be overcome via the concurrent depletion of tumour cells and of major types of immunosuppressive cells via a monoclonal antibody binding the enzyme CD73 (which we identified is highly expressed on tumour cells and on regulatory T cells, myeloid-derived suppressor cells and tumour-associated macrophages, yet not on cytolytic T lymphocytes, natural killer cells and dendritic cells). In mice with murine tumours, the systemic administration of anti-PD1 antibodies and anti-CD73 antibodies conjugated to a near-infrared dye subverted near-infrared-irradiated tumours from acquiring resistance to ICB and resulted in the eradication of advanced tumours. The elimination of immunosuppressive cells may overcome acquired resistance to ICB across a range of tumour types and combination therapies.”

8、Batf3+ DCs and the 4–1BB/4–1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy
Andrea Ziblat,et al.Cell Rep. 2024.PMCID: PMC11229087
“The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4–1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8+ T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3+ DCs and CD8+ T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to Batf3+ DCs within the TME is associated with CD8+ T cell transcriptional states linked to anti-PD-1 response. Our results demonstrate that Batf3+ DCs within the TME are critical for PD-1/PD-L1 blockade efficacy and indicate a major role for the 4–1BB/4–1BB ligand (4–1BBL) axis during this process.”

9、Immunomodulatory monoclonal antibodies combined with peptide vaccination provide potent immunotherapy in an aggressive murine neuroblastoma model
Emily L Williams,et al.Clin Cancer Res. 2014.PMCID: PMC3743027
“Purpose
Neuroblastoma is one of the commonest extra-cranial tumors of childhood. The majority of patients present with metastatic disease for which outcome remains poor. Immunotherapy is an attractive therapeutic approach for this disease, and a number of neuroblastoma tumor antigens have been identified. Here we examine the therapeutic potential of combining immunomodulatory monoclonal antibodies (mAb) with peptide vaccination in murine neuroblastoma models.
Experimental design
Neuroblastoma bearing mice were treated with mAb targeting 4-1BB, CD40 and CTLA-4 alone, or in combination with a peptide derived from the tumor antigen survivin (GWEDPPNDI). Survivin-specific immune response and therapeutic efficacy was assessed.
Results
In the Neuro2a model, treatment of established tumor with either anti-4-1BB, anti-CD40 or anti-CTLA-4 mAb results in tumor regression and long-term survival in 40-60% of mice. This is dependent on NK and CD8+ T cells and is associated with tumor CD8+ lymphocyte infiltrate. Successful therapy is achieved only if mAb is given to mice once tumors are established, suggesting dependence on sufficient tumor to provide antigen. In the more aggressive AgN2a and NXS2 models, single agent mAb therapy provides ineffective therapy. However if mAb (anti-CTLA-4) is given in conjunction with survivin peptide vaccination then 60% long term survival is achieved. This is associated with the generation of survivin-specific T cell immunity, which again is only demonstrated in the presence of tumor antigen.
Conclusions
These data suggest the combination of antigen and co-stimulatory mAb may provide effective immunotherapy against neuroblastoma and may be of particular use in the minimal-residual disease setting.”

10、4-1BB Agonism Combined With PD-L1 Blockade Increases the Number of Tissue-Resident CD8+ T Cells and Facilitates Tumor Abrogation
Qiu-xia Qu,et al.Front Immunol. 2020.PMCID: PMC7193033
“Although the milestone discovery of immune checkpoint blockade (ICB) has been translated into clinical practice, only a fraction of patients can benefit from it with durable responses and subsequent long-term survival. Here, we tested the anti-tumor effect of combining PD-L1 blockade with 4-1BB costimulation in 3LL and 4T1.2 murine tumor models. Dual treatment induced further tumor regression and enhanced survival in tumor-bearing mice more so than PD-L1 and 4-1BB mAb alone. It was demonstrated that dual anti-PD-L1/anti-4-1BB immunotherapy increased the number of intratumoral CD103+CD8+ T cells and altered their distribution. Phenotypically, CD103+CD8+ T cells expressed a higher level of 4-1BB and PD-1 than their CD103− counterparts. Administration of PD-L1 mAb and 4-1BB mAb further increased the cytolytic capacity of CD103+CD8+ T cells. In vivo, CD103−CD8+ T cells could differentiate into CD103+CD8+ progeny cells. In a human setting, more CD8+ T cells differentiated into CD103+CD8+ T cells in the peripheral tumor region of lung cancer tissues than in the central tumor region. Collectively, infiltrated CD103+CD8+ T cells served as a potential effector T cell population. Combining 4-1BB agonism with PD-L1 blockade could increase tumor-infiltrated CD103+CD8+T cells, thereby facilitating tumor regression.”

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: LOB12.3)

Anti-mouse CD137 Antibody (3H3) from: Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody(Clone: 3H3): PA007276.r2a Syd Labs

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