About RecombiMAb anti-mouse TREM-2 (LALA-PG) The 178-CP067 monoclonal antibody is a chimeric version of the original 178 antibody. The variable domain sequences are identical to the original 178-CP067 but the constant region sequences have been switched from rat IgG2a to mouse IgG2a. The 178-CP067 antibody also contains a LALA-PG mutation in the Fc fragment rendering it unable to bind to endogenous Fcγ receptors. The 178-CP067 monoclonal antibody reacts with mouse TREM-2 (the triggering receptor expressed on myeloid cell 2), a single-pass transmembrane protein also known as PLOSL2. This anti-mouse TREM-2 antibody does not cross-react with TREM-1. TREM-2 is primarily expressed by myeloid cells, infiltrating macrophages, and tissue-specific macrophages, including microglia. TREM-2 acts as a receptor for abeta 42 (a cleavage product of the amyloid beta precursor protein) and mediates its uptake and degradation in microglia. TREM-2 also binds to lipoproteins (LDL, VLDL, and HDL) and apolipoproteins (APOA1/A2, APOB, APOEs, and others) and enhances their uptake by microglial cells. TREM-2 plays a key role in the functions of microglia, such as phagocytosis, cytokines release, lipid sensing, and microglia proliferation and migration. TREM2 has both anti-inflammatory and pro-inflammatory effects. In in vivo models of Alzheimer's disease (AD), TREM2 serves as a reliable indicator of microglial activation, and mutations in TREM-2 have been associated with an increased risk of neurodegenerative diseases like AD, ALS, and Parkinson's disease (PD). Tumor-infiltrating macrophages and various types of cancer cells also express TREM2 at varying levels in cancers. TREM-2 suppresses anti-tumor immune responses by inhibiting T cell-mediated immune responses and through its effects on NK cell-mediated anti-tumor immunity. In tumor immune microenvironment (TME), TREM2 is a key regulator, and its blockade can promote the response to anti-PD1 therapy. This recombinant anti-mouse TREM-2 (antibody has been shown to block TREM-2 signals in vivo in murine tumor models. RecombiMAb anti-mouse TREM-2 (LALA-PG) Specifications IsotypeMouse IgG2a, κ Recommended Isotype Control(s)RecombiMAb mouse IgG2a (LALA-PG) isotype control, unknown specificity Recommended Dilution BufferInVivoPure pH 7.0 Dilution Buffer ImmunogenRecombinant protein containing the ectodomain of TREM-2 fused to the constant domain of human Ig Reported Applicationsin vivo TREM-2 blockade in vitro TREM-2 blockade Flow cytometry FormulationPBS, pH 7.0 Contains no stabilizers or preservatives Endotoxin<1EU/mg (<0.001EU/μg) Determined by LAL gel clotting assay Aggregation<5% Determined by SEC Purity>95% Determined by SDS-PAGE Sterility0.2 μm filtration ProductionPurified from HEK293 cell supernatant in an animal-free facility PurificationProtein G Molecular Weight150 kDa StorageThe antibody solution should be stored at the stock concentration at 4°C. Do not freeze. Application ReferencesRecombiMAb anti-mouse TREM-2 (LALA-PG) (CLONE: 178-CP067)Sun R, Han R, McCornack C, Khan S, Tabor GT, Chen Y, Hou J, Jiang H, Schoch KM, Mao DD, Cleary R, Yang A, Liu Q, Luo J, Petti A, Miller TM, Ulrich JD, Holtzman DM, Kim AH (2023). "TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma" Sci Adv 9(19):eade3559. PubMedTriggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased tumor growth and increased survival. Trem2 inhibition reprogrammed myeloid phenotypes and increased programmed cell death protein 1 (PD-1)+CD8+ T cells in the TME. Last, Trem2 deficiency enhanced the effectiveness of anti-PD-1 treatment, which may represent a therapeutic strategy for patients with GBM.Molgora M, Esaulova E, Vermi W, Hou J, Chen Y, Luo J, Brioschi S, Bugatti M, Omodei AS, Ricci B, Fronick C, Panda SK, Takeuchi Y, Gubin MM, Faccio R, Cella M, Gilfillan S, Unanue ER, Artyomov MN, Schreiber RD, Colonna M (2020). "TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy" Cell 182(4):886-900.e17. PubMedCheckpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer's disease. TREM2 is also expressed by tumor-infiltrating macrophages. Here, we found that Trem2-/- mice are more resistant to growth of various cancers than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses. TREM2 was expressed in tumor macrophages in over 200 human cancer cases and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy.
