Anti-Mouse 4-1BB (CD137) – Purified in vivo GOLD™ Functional Grade

Mouse CD137 human Fc fusion protein

This monoclonal antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Functional grade preclinical antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

Activity is directed against mouse 4-1BB (CD137), a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily. Clone LOB12.3 recognizes an epitope on the extracellular domain of 4-1BB and is widely characterized as an agonistic antibody that triggers receptor signaling, though its potency is often dependent on Fc receptor (FcγR) cross-linking¹.

4-1BB (CD137) is a potent costimulatory receptor that plays a critical role in sustaining effective T cell immune responses and generating immunological memory. Under resting conditions, 4-1BB expression is negligible; however, it is rapidly upregulated following T cell receptor (TCR) stimulation². The natural ligand for 4-1BB is 4-1BBL (TNFSF9), which is expressed on professional antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells⁴.

Upon ligation, 4-1BB recruits TNFR-associated factors (TRAF1 and TRAF2) to its cytoplasmic tail. This assembly forms a signalosome that activates the NF-κB, c-Jun N-terminal kinase (JNK), and p38 MAPK signaling pathways⁵. These signals synergize with TCR signaling to upregulate anti-apoptotic proteins (e.g., Bcl-xL, Bfl-1) and promote the robust proliferation and survival of effector CD8+ T cells^1,3.

Clone LOB12.3 is a well-established agonistic antibody used to study 4-1BB biology and cancer immunotherapy. Unlike the 3H3 clone (which is a stronger intrinsic agonist), LOB12.3 typically requires cross-linking by Fcγ receptors on host cells to achieve maximal receptor clustering and signaling¹. This requirement makes LOB12.3 a valuable tool for investigating the mechanisms of antibody-dependent costimulation and evaluating safety profiles, as stronger agonists can sometimes lead to hepatotoxicity⁶. Research has demonstrated that LOB12.3 administration can enhance tumor rejection and increase the ratio of effector T cells to regulatory T cells in the tumor microenvironment^1,6.

4-1BB is an inducible costimulatory receptor expressed primarily on activated CD4+ and CD8+ T cells and Natural Killer (NK) cells². It is also found on activated dendritic cells (DCs), mast cells, and regulatory T cells (Tregs)³.

Receptor: 4-1BB / Ligand: 4-1BBL (TNFSF9)

1. Bartkowiak T, Curran MA. 4-1BB Agonists: Multi-Potent Potentiators of Tumor Immunity. Front Oncol. 5:117. 2015.
2. Vinay DS, Kwon BS. 4-1BB signaling beyond T cells. Cell Mol Immunol. 8(4):281-284. 2011.
3. Melero I, Hirschhorn-Cymerman D, Morales-Kastresana A, Sanmamed MF, Wolchok JD. Agonist antibodies to TNFR molecules that costimulate T and NK cells. Clin Cancer Res. 19(5):1044-1053. 2013.
4. Croft M. Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol. 3(8):609-620. 2003.
5. Zapata JM, Perez-Chacon G, Carr-Baena P, et al. CD137 (4-1BB) Signalosome: Complexity Is a Matter of TRAFs. Front Immunol. 9:2618. 2018.
6. Bartkowiak T, Jola S, Aldrich M, et al. Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine. Proc Natl Acad Sci U S A. 112(38):E5290-E5299. 2015.