PA007276.r2a: In vivo Grade Recombinant Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody, Rat IgG2a Kappa (Clone: 3H3)
Recombinant rat IgG2a Monoclonal Antibody.
Clone: 3H3.
Isotype: Rat IgG2a kappa.
Source: The anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: 3H3) was produced in mammalian cells.
Specificity/Sensitivity: The in vivo grade recombinant mouse 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 antibody 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.
Background
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 of anti-mouse CD137 (TNFRSF9 or 4-1BB) antibody (3H3)
Differentiated agonistic antibody targeting CD137 eradicates large tumors without hepatotoxicity.
Madireddi S, et al. (2020). J Clin Invest. 2020 Mar 12;130(6):3090-3103. doi: 10.1172/JCI133647. PMID: 32161196
In order to understand the effect of epitope and in vitro potency on in vivo activity, we compared CTX-471-AF with the urelumab-like mouse surrogate antibody 3H3 (anti-mouse CD137). To assess the potential of CTX-471, CTX-471-AF, and 3H3 to induce liver inflammation, we administered up to 80 mg/kg of these antibodies to nontumor-bearing mice by weekly i.v. injections. Comparison studies were performed against anti-CD137 clone 3H3 and a panel of well-characterized immuno-oncology antibodies targeting PD-1, PD-L1, CTLA-4, or OX40 that have demonstrated activity against smaller CT-26 tumors in the literature (Figure 8, B and C). The 3H3 antibody displayed superagonist activity in the mouse assay, further supporting its use as a functional surrogate for urelumab. In the CT-26 murine colon carcinoma model, both CTX-471-AF and CTX-471 demonstrated potent antitumor activity across a broad dose-range in mice bearing established (50–75 mm³) tumors (Figure 4A and Supplemental Figure 3A), resulting in a high rate of complete cures and significantly improved overall survival (Figure 4B and Supplemental Figure 3B).
Tags: anti-mouse CD137; anti-mouse CD137 3H3
Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity.
Zhang H, et al. (2019). MAbs. 2019 May 4;11(4):706-719. doi: 10.1080/19420862.2019.1599692. PMID: 31105267
Both LOB12.3 and 3H3 Abs (anti-mouse CD137) 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). We observed similarly increased ALT levels in 3H3-treated naive mice (Fig. 1e, f), suggesting 3H3-induced liver toxicity is independent of tumor burden. Besides elevation of ALT in serum, we also found that immune cell infiltration in the liver of 3H3-treated mice (Fig. 1g). Our data suggested anti-4-1BB Ab-induced anti-tumor activity and liver toxicity could be separated in natural anti-4-1BB Abs. We, therefore, used LOB12.3 and 3H3 Abs as tool molecules to investigate the underlying mechanism in order to gain insights for clinical development of agonistic anti-4-1BB Abs.
Tags: anti-mouse CD137 3H3 antibody in vivo; anti-mouse CD137 3H3 antibody in animal model
Gp96-Ig/Costimulator (OX40L, ICOSL, or 4-1BBL) Combination Vaccine Improves T-cell Priming and Enhances Immunity, Memory, and Tumor Elimination.
Nicodemus LF, et al. (2016). Cancer Immunol Res. 2016 Sep;4(9):766-78. doi: 10.1158/2326-6066.CIR-16-0063. PMID: 27364122
For Ova/OT-I experiments performed using 3T3 cell lines, mice on days 0 and 35 (in the case of boosted mice) were either untreated, vaccinated with the 3T3-ova parental clone as a control, vaccinated with Im PACT (alone or in combination with 100 µg of agonist antibodies to ICOS), 4-1BB (3H3 antibody, anti-mouse CD137), or OX40 (OX86 antibody; Supplementary Fig. S1F), or vaccinated with all Com PACT versions (Com PACT/OX40L, Com PACT/ICOSL, or Com PACT/4-1BBL). Vaccination with 3T3-Im PACT cells led to proliferation of OT-I cells (prime response) between 4 and 7 days after vaccination, which corresponded to ~10% of the total peripheral blood CD8+ T cells. This OT-I response was doubled (~20%) by coadministration of an OX40 agonist mAb, but not with ICOS or 4-1BB costimulatory mAbs (Fig. 1B). Interestingly, the addition of a 4-1BB agonist mAb resulted in a significant increase in FOXP3+ regulatory T cells (Treg), which is consistent with previous findings (26). Mice treated with Com PACT/OX40L generated significantly greater numbers of CD4+, CD8a+, and SIINFEKL+ CD8+ cells at the site of vaccination in the peritoneal cavity (Supplementary Fig. S5A).
Tags: anti-mouse CD137 3H3 in cancer research; anti-mouse CD137 3H3 in mouse tumor model
A human monoclonal IgG that binds Aβ assemblies and diverse amyloids exhibits anti-amyloid activities in vitro and in vivo.
Patterson S, et al. (2015). J Neurosci. 2015 Apr 22;35(16):6275-88. doi: 10.1523/JNEUROSCI.5109-14.2015. PMID: 25904780
We cloned one of these antibodies, 3H3 (anti-mouse CD137 antibody), from memory B cells of a healthy individual using a hybridoma method. Functional studies showed that 3H3 (inhibits both Aβ and LC amyloid formation in vitro and abrogates disruption of hippocampal synaptic plasticity by AD-patient-derived soluble Aβ in vivo. A 3H3 single-chain variable fragment (scFv) retained the binding specificity of the 3H3 IgG and, when expressed in the brains of transgenic mice using an adeno-associated virus (AAV) vector, decreased parenchymal Aβ amyloid deposition in TgCRND8 mice and ADan (Danish Amyloid) cerebral amyloid angiopathy in the mouse model of FDD. For adult injections, mAb 3H3 (500 μg, 1 mg/ml) was administered though intraperitoneal injection to TgCRND8 mice. In the live rat model of hippocampal LTP, 3H3 abrogated the synaptotoxicity of soluble Aβ oligomers contained in an AD-brain extract.
Tags: function of anti-mouse CD137 3H3; bioactivity of anti-mouse CD137 3H3 antibody
Scintigraphic detection of xenografted tumors producing human basic fibroblast growth factor in vivo.
Kobayashi H, et al. (1993). Cancer Immunol Immunother. 1993 Sep;37(4):281-5. doi: 10.1007/BF01518449. PMID: 8402731
A murine monoclonal antibody 3H3 recognizes the basic fibroblast growth factor (FGF) and inhibits the growth of human glioblastoma cells both in vitro and in vivo. We studied the potential of a scintigraphic technique using the 3H3 antibody (anti-mouse CD137 antibody) to detect tumors that produce basic FGF. 125I- and 111In-labeled 3H3 bound to U87MG human glioblastoma cells in vitro. A high level of radioactivity from 3H3 was retained at the tumor, whereas an irrelevant antibody cleared rapidly from the injected site. Radiolabeled 3H3 was not retained in tumors that did not produce basic FGF.
Tags: anti-mouse CD137 3H3 antibody of low endotoxin; anti-mouse CD137 (3H3)
For more references about anti-mouse CD137 (TNFRSF9 or 4-1BB) antibody (3H3), please contact our scientific support team with message@sydlabs.com.
Related Recombinant IgG Reference Antibodies:
Recombinant rat lgG2a 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)