PA007275.r1: In vivo Grade Recombinant Anti-mouse CD137 (TNFRSF9 or 4-1BB) Monoclonal Antibody, Rat IgG1 Kappa (Clone: LOB12.3)
Recombinant rat IgG1 Monoclonal Antibody.
Clone: LOB12.3.
Isotype: Rat IgG1 kappa.
Source: The anti-mouse CD137 (TNFRSF9 or 4-1BB) monoclonal antibody (clone: LOB12.3) was produced in mammalian cells.
Specificity/Sensitivity: The in vivo grade recombinant rat 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 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 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 of anti-mouse CD137 (TNFRSF9 or 4-1BB) antibody (LOB12.3)
Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity.
Qi X, et al. Nat Commun. 2019 May 22;10(1):2141. doi: 10.1038/s41467-019-10088-1. PMID: 31105267
We, therefore, used LOB12.3 (anti-mouse CD137) 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. LOB12.3 and 3H3 are commercially available rat monoclonal antibodies that bind specifically to murine CD137 and can agonize the activity of this receptor. Our data suggested anti-4-1BB Ab-induced anti-tumor activity and liver toxicity could be separated in natural anti-4-1BB Abs. 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). We observed similarly increased ALT levels in 3H3-treated naive mice (Fig. 1e, f), suggesting 3H3-induced liver toxicity is independent of tumor burden.
Tags: anti-mouse CD137 LOB12.3; anti-mouse CD137 LOB12.3 antibody
CD137/OX40 Bispecific Antibody Induces Potent Antitumor Activity that Is Dependent on CD8+ T Cells, CD4+ T Cells, and Conventional Type 1 Dendritic Cells.
Gaspar M, et al. Cancer Immunol Res. 2021 Mar;9(3):325-338. doi: 10.1158/2326-6066.CIR-20-0580. PMID: 33355299
anti-mouse CD137 (mCD137(Lob12.3) WT mAb; clone Lob12.3 (3)) and anti-mouse CD137 (mCD137(3H3) WT mAb; clone 3H3 (24)) all in human IgG1 format, with (mAb) or without (WT mAb) LALA mutations. No activity of the CD137 antibody was detected in this assay, but in DO11.10 T cell line expressing mouse CD137 and stimulated with coated anti-mouse CD3 antibody, clone Lob12.3 increased IL2 production in the presence of crosslinking (Supplemental Fig. S6B). The OX40 (clone OX86) or CD137 (clone Lob12.3) control antibodies with human IgG1 isotype or their combination showed no antitumor activity (Fig. 4B), unlike previously published results using the original rat versions of these antibodies (3). The results showed a clear difference between the two CD137 agonist antibodies tested, clone 3H3 induced a sustained increase in T cell infiltration, proliferation and activation in the liver and spleen, whereas clone Lob12.3 did not (Fig. 6B). When these antibodies were tested in a model DO11.10 T cell line expressing human CD137 and stimulated with coated anti-mouse CD3 antibody, Fab clone 20H4.9 also showed crosslink-independent activity, whereas Fab clones FS30 and MOR7480.1 did not (Supplemental Fig. S6A).
Tags: anti-mouse CD137 LOB12.3 antibody in vivo; anti-mouse CD137 LOB12.3 antibody in animal model
4-1BB Agonism Combined With PD-L1 Blockade Increases the Number of TCF-1+ Progenitor Exhausted CD8 T Cells in Tumor-Infiltrating Lymphocytes.
Galand C, et al. Front Immunol. 2020 Mar 24;11:497. doi: 10.3389/fimmu.2020.00497. PMID: 32269077
Tumor bearing mice were randomized into four treatment cohorts: (i) control IgG; (ii) PD-L1 mAb (clone 10F.9G2); (iii) 4-1BB mAb (clone LOB12.3); or (iv) PD-L1 mAb combined with 4-1BB mAb. All antibodies were administered at a dose of 150 μg/mouse through intraperitoneal injection twice per week. As shown in Figures 1A,B, anti-PD-L1 mAb alone failed to control 3LL tumor growth, treatment with anti-4-1BB mAb only partially inhibited the tumor growth, but almost complete inhibition of tumor growth in mice was seen in the combination therapy group (P < 0.01). Notably, there was a distinction between combinatorial therapy and other groups in terms of the ratio of infiltrated CD103+ CD8+ T cells (P < 0.05, Figure 2). Strikingly, anti-4-1BB mAb (LOB12.3) combined with anti-PD-L1 mAb could significantly enhance the capacity of CD103+ CD8+ T cells to lyse target cells (P < 0.05), whereas, cytolytic capacity of CD103− CD8+ T cell was little affected by this treatment.
Tags: anti-mouse CD137 LOB12.3 in cancer research; anti-mouse CD137 LOB12.3 mAb in cancer research
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
We demonstrate that therapy with an agonist 4-1BB mAb (LOB12.3) is uniquely capable of promoting regression of established HPV+ TC-1 tumors when combined with an E6/E7 peptide vaccine. Mice were treated with anti-4-1BB (LOB12.3) or rat IgG isotype control on days 7, 10, and 13 post-tumor implantation. Flow cytometry analysis showed increased CD8+ T cell infiltration in tumors treated with LOB12.3. The combination therapy led to complete tumor regression in 70% of mice. Survival was monitored for 60 days post-treatment.
Tags: function of anti-mouse CD137 LOB12.3; bioactivity of anti-mouse CD137 LOB12.3
Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production.
Curran MA, et al. PLoS One. 2011 May 4;6(5):e19499. doi: 10.1371/journal.pone.0019499. PMID: 21559362
Antibodies Anti-CTLA-4 (9D9), a 4-1BB (LOB12.3) [12], Rat Ig and mIgG2b used in vivo were produced by... Dosing per injection was 100 ug 9D9, 350 ug LOB12.3, 350 ug RatIg, and 100 ug mIgG2b. Staining antibodies included CD4-Q605, CD8-Pacific Orange, CD3-APCAlexa750 - Invitrogen. CD4-APC, FoxP3 Pacific Blue, KLRG1-APC, PD-1-FITC, 4-1BB-biotin - eBioscience. CD8-PE, IFN- c -PE-CY7, Ki67-FITC, TNF a -APC.
Tags: anti-mouse CD137 LOB12.3 of low endotoxin; anti-mouse CD137 (LOB12.3)
For more references about anti-mouse CD137 (TNFRSF9 or 4-1BB) antibody (LOB12.3), please contact our scientific support team with message@sydlabs.com.
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)