MAbMods™ Anti-Mouse TREM2 [Clone 178 (LALAPG)] — Fc Muted™

In Vivo Applications of Clone 178 (LALAPG) in Mice

Clone 178 (LALAPG) refers to a recombinant, Fc-muted (LALAPG) monoclonal antibody specific for mouse TREM2 (Triggering Receptor Expressed on Myeloid cells 2). Its engineered Fc region prevents effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement activation, allowing it to block TREM2 signaling without depleting TREM2-expressing cells in vivo.

Common In Vivo Applications

Cancer Immunotherapy Research
Clone 178 (LALAPG) has been used to interrogate the role of TREM2 in tumor biology and the tumor immune microenvironment. In murine tumor models, systemic administration of this antibody has been shown to remodel the myeloid cell landscape within tumors, leading to reduced tumor growth and enhanced sensitivity to checkpoint blockade therapies such as anti-PD-1. The antibody blocks TREM2-mediated signals in tumor-associated macrophages, thereby promoting anti-tumor immune responses without depleting these cells directly. This makes it a valuable tool for studying the mechanistic impact of TREM2 blockade on tumor immunity.

Neuroimmunology and Neurodegenerative Disease Models
TREM2 is highly expressed on microglia in the central nervous system (CNS). While direct in vivo applications in neurodegeneration models (e.g., Alzheimer’s disease) are not detailed in the provided search results, the antibody’s specificity and blocking (non-depleting) activity position it as a candidate for investigating TREM2’s role in microglial function, neuroinflammation, and phagocytosis in vivo. It could be used to test hypotheses about TREM2’s contribution to disease progression or resolution in CNS pathologies.

General Immunology and Myeloid Cell Biology
Given TREM2’s broad expression on myeloid cells—including macrophages, microglia, osteoclasts, and some tissue-specific macrophages—clone 178 (LALAPG) can be employed to study the in vivo function of TREM2 in various immunological contexts beyond cancer, such as infection, autoimmunity, and metabolic disease. Its blocking (rather than depleting) nature allows researchers to distinguish between the signaling and survival functions of TREM2-bearing cells.

Key Features Enabling In Vivo Use

• Fc Silencing: The LALAPG mutation in the Fc region eliminates binding to Fcγ receptors and complement, preventing unwanted cell depletion or activation via these pathways.
• Specific Blocking Activity: The antibody blocks ligand (e.g., HDL) binding to TREM2 and inhibits downstream signaling without reducing the number of TREM2+ cells.
• Broad Compatibility: It is suitable for a range of in vivo applications including tumor models, neuroimmunology, and general myeloid cell biology.
• Preclinical Tool: It is classified as a research-use-only reagent, not for diagnostic or therapeutic use in humans.

Example Protocol

A typical in vivo protocol involves intraperitoneal (i.p.) injection of the antibody (e.g., 200 μg/mouse every 5 days) starting shortly after tumor implantation, allowing longitudinal assessment of tumor growth and immune modulation.

Summary Table: In Vivo Applications of Clone 178 (LALAPG)

Clone 178 (LALAPG) is thus a versatile, mechanism-focused tool for in vivo studies of TREM2 biology across multiple disease models, particularly where distinguishing signaling blockade from cell depletion is critical.

Other commonly used antibodies or proteins in the literature with 178 (LALAPG) include wild-type IgG1, LALA mutants, aglycosylated IgGs, and various other combinatorial Fc mutants.

Key protein/antibody variants used with or for comparison to 178 (LALAPG):

• Wild-type IgG1: Has a native Fc region and is the baseline for assessing Fc-dependent immune effects.
• LALA mutant (L234A/L235A): Double mutation reducing FcγR and C1q binding—used when lower effector function is desired but does not fully silence FcγR interactions.
• Aglycosylated IgG: Lacks Fc glycan and further dampens Fc-effector interactions, sometimes compared in studies dissecting Fc requirements.
• Other combinatorial Fc mutants: Includes additional mutations like LALAPG (L234A/L235A/P329G) for enhanced silencing of FcγR and complement binding while leaving FcRn interactions intact.
• Fc Muted™ variants (including 178 LALAPG): Used for applications requiring minimal effector function, commonly in studies of immune function and receptor blockade.

Additional context:

• Therapeutic antibodies engineered with LALAPG or similar mutations that have entered clinical trials include cergutuzumab, cibisatamab, faricimab, RG7386, bimagrumab, cemiplimab, galcanezumab, progolimab, risankizumab, spesolimab, teplizumab.
• Plant-derived Fc-effector-silent antibodies, such as Durvalumab LALAPG, are used for functional studies where immune suppression is required.
• Studies sometimes reference antibodies with less common Fc modifications affecting glycosylation, allotypic variation, or additional substitutions for fine-tuned Fc interaction control.

These variants are frequently used in functional assays (e.g., blocking, receptor-binding, in vivo models) to investigate the biological role of Fc interactions, specificity, and therapeutic efficacy.

Key findings from scientific citations of clone 178 (LALAPG) primarily highlight its use as a specialized research antibody for selective blockade of TREM2 function in studies of immunology, neurodegeneration, and cancer biology, particularly with minimized immune effector functions.

Essential context and supporting details:

• Selectivity and Mechanism: Clone 178 (LALAPG) is engineered with an Fc-mutated LALAPG domain that eliminates Fc receptor and complement binding, thereby “muting” its effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADCP). This design ensures any observed biological effects are due to TREM2 blockade, not Fc-mediated immune activation.

• Neurodegeneration Studies: In models of Alzheimer’s disease, TREM2 signaling is implicated in sustaining microglial activation and disease pathology. Clone 178 has been used to demonstrate that blocking TREM2 modulates disease-relevant myeloid cell responses and can alter disease progression in preclinical models.

• Cancer Biology: TREM2 expression on tumor-infiltrating macrophages supports immunosuppressive environments in cancers. Blocking TREM2 with clone 178 increases responsiveness to checkpoint immunotherapies like anti-PD-1 in mouse models and reduces tumor growth, sometimes in synergy with other immunotherapies.

• Experimental Design: Because clone 178 (LALAPG) is non-depleting, it allows for the study of TREM2’s role without the confounding effects of depleting myeloid cell populations. It has been used in both in vitro and in vivo mouse studies to clarify TREM2-dependent signaling and function.

• Immunotherapy Context: Clone 178 has also been used comparatively with other checkpoint antibodies (e.g., anti-CTLA-4 and anti-PD-1) to dissect the interplay between TREM2 blockade and cancer immunotherapy effectiveness.

• Molecular Engineering: The antibody was derived by immunizing rats with recombinant TREM2, followed by molecular grafting of its variable region onto a mouse IgG2a Fc backbone with the LALAPG mutation. It does not cross-react with TREM1, ensuring target specificity.

• Cited References and Studies: Key supporting studies include works by Molgora et al. (Cell, 2020), Deczkowska et al. (Cell, 2020), and Keshari et al. (Cell Reports, 2024), among others. These publications demonstrate its application in diverse mouse models addressing tumor immunity, neurodegeneration, and TREM2-driven pathology.

• Typical Applications: The antibody is commonly used in preclinical models for targeted blockade of TREM2, especially to:

  • Study neuroinflammation and neurodegeneration mechanisms.
  • Explore myeloid cell remodeling in tumors.
  • Test combined immunotherapeutic approaches.
  • Minimize artifacts in functional assays due to Fc effector functions.

In summary, clone 178 (LALAPG) is recognized as a critical tool for dissecting TREM2 biology, especially where Fc-mediated mechanisms would otherwise confound interpretation. It has enabled advances in understanding TREM2 in neurodegenerative disease models and tumor immunology, often serving as the standard for TREM2 functional blockade in murine studies.

Dosing Regimens of Clone 178 (LALAPG) in Mouse Models

Clone 178 (LALAPG) is a monoclonal antibody targeting mouse TREM2, engineered with an Fc-muted LALA-PG mutation to reduce effector functions such as FcγR binding. While specific studies using this exact clone are limited, available data and manufacturer guidelines provide insights into dosing variability.

Standard Reported Dose

• Consistent Dose Across Models: The dose for clone 178 (LALAPG) is typically 250 μg per injection in most mouse models.
• Published Example: One published preclinical study using a related clone (178, not explicitly Fc-muted) administered 200 μg/mouse intraperitoneally every 5 days, starting from day 2 after tumor injection in a cancer model. This suggests that, even for closely related antibodies, doses in the 200–250 μg range are commonly used.

Variability Across Disease Models

• Disease-Specific Adjustments: Although the dose per injection tends to be consistent, the frequency and duration of administration may be adapted based on the specific disease model (e.g., neuroinflammation, cancer, metabolic disease) and the kinetics of the disease process or outcome measures being studied.
• Route of Administration: Intraperitoneal (IP) injection is the standard route for in vivo studies.
• No Publicly Available Model-Specific Protocols: There is no comprehensive, publicly accessible database detailing dosing schedules for clone 178 (LALAPG) across all possible mouse models. Most available information is either generalized or from a single published study.

General Guidance for Antibody Dosing in Mice

• Typical Range: For most in vivo monoclonal antibody applications in mice, doses range from 100–500 μg per injection, with 200–250 μg being common for checkpoint and receptor-blocking antibodies.
• Frequency: Dosing intervals often range from every 3–5 days, depending on the half-life of the antibody and the dynamics of the target.
• Model-Dependent Optimization: The optimal regimen (dose, frequency, duration) should be empirically determined for each experimental context, considering the antibody’s pharmacokinetics, the disease model’s progression, and the desired biological effect.

Summary Table

Key Points

• Clone 178 (LALAPG) is most often dosed at 250 μg per injection in mouse models, but the regimen (frequency, duration) should be tailored to the specific experimental context.
• Published studies using related clones suggest similar doses (200–250 μg) and typical frequencies (e.g., every 5 days).
• No broad, model-specific dosing tables are publicly available; optimization is recommended for each study.
• Always consult the latest literature and consider pilot experiments to establish the optimal regimen for your specific model and research question.