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

Clone 178 (LALAPG) is a recombinant monoclonal antibody targeting mouse TREM2 that is specifically engineered for in vivo mouse studies to block TREM2 function without engaging Fc receptor-mediated immune effector functions.

Key points about its use and functional properties:

• Fc Muted (LALAPG) Mutation: The LALAPG mutations in the Fc domain abolish binding to Fc? receptors and complement, minimizing antibody-dependent cellular cytotoxicity and antibody-dependent phagocytosis. This ensures that in vivo effects are due to specific TREM2 blockade, not off-target immune activation.

• Mechanism in vivo: Clone 178 (LALAPG) is used to block ligand binding to TREM2 on myeloid cells, including microglia and tumor-infiltrating macrophages, thereby inhibiting TREM2-mediated signaling pathways.

• Research context and disease models:

  • Frequently used in cancer and neuroimmunology models, including tumor immunology studies to investigate the role of TREM2+ macrophages in the tumor microenvironment and their impact on responses to immunotherapies like anti-PD1.
  • In cancer models, it has been used in vivo for TREM2 blockade, not cell depletion, allowing researchers to study non-depleting, functional inhibition of TREM2.
  • Relevant for neuroscience research, including Alzheimer’s disease and other neurodegenerative disease models involving microglial function and innate immune responses.

• Typical in vivo procedure:

  • Administered to mice (doses in literature example: 250??g per injection) to block TREM2 function during disease or immunotherapy trials, enabling assessment of the antibody’s impact on disease progression and immune cell behavior.
  • As a blocking/non-depleting antibody, it does not result in the global depletion of TREM2-expressing cells, allowing for specific mechanistic interrogation of TREM2 signaling.

• Validation and formulation:

  • Supplied as endotoxin-low, aseptic, and carrier-free for preclinical studies.
  • Validated for functional blocking in vivo, as well as in ELISA, flow cytometry, and other assays.

In summary, clone 178 (LALAPG) is used in vivo in mice as a highly specific, Fc silenced antibody that permits the study of TREM2’s role in immunity and disease—with blocking, not depleting, activity—facilitating precise mechanistic experiments in cancer, CNS, and other immunological models.

The 178 (LALAPG) antibody variant is commonly used alongside other Fc-silenced or Fc-engineered antibodies that are designed to lack immune effector functions, especially in studies seeking to block receptor function without Fc? receptor or complement activation.

Some commonly referenced Fc-engineered antibody designs and proteins used in the literature with or in comparison to 178 (LALAPG) include:

• Wild-type IgG1 antibodies: Standard form for comparison of effector function and binding.
• LALA (L234A/L235A) mutants: Another popular Fc-silenced variant, though it still shows some residual Fc?R binding compared to LALAPG.
• Aglycosylated (Agly) antibodies: Lacking Fc glycosylation to reduce Fc?R and complement binding.
• Other triple or combinatorial Fc mutants: For instance, variants with additional mutations at G236 or combinations designed to further minimize receptor binding (e.g., L234X/L235X/G236R).
• Specific examples from clinical and preclinical studies:
  • Cergutuzumab, cibisatamab, faricimab, RG7386: Clinical-stage antibodies that utilize the LALAPG Fc mutation as a model for complete silencing of effector function.
  • Rituximab (CD20), muromonab (CD3), alemtuzumab (CD52): These therapeutic antibodies have been expressed with various Fc mutations (including LALAPG) to compare functional outcomes and binding behavior.
  • Human Contraception Antibody (HCA): Engineered with LALAPG for specialized applications.

Frequently, LALA, LALAPG, aglycosylated antibodies, and wild-type IgG1 are included together in experimental sets to compare the impact of different Fc engineering strategies on functions such as Fc?R binding, complement activation, or downstream biological effects.

Summary Table: Commonly Used Antibodies/Proteins with LALAPG

These antibodies and Fc-engineered proteins are often compared in head-to-head receptor-binding experiments and used to dissect the role of IgG Fc interactions in a variety of immunological assays and disease models.

Key findings from citations of clone 178 (LALAPG) in the scientific literature primarily relate to its use as a research tool for selectively blocking TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) function in both immunology and cancer biology, while minimizing confounding immune effector functions. The main points are:

• Clone 178 (LALAPG) is an anti-mouse TREM2 antibody engineered to block TREM2 ligand binding without cross-reactivity to TREM1 and with a LALAPG mutation that abrogates Fc receptor and complement binding. This minimizes antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis, allowing researchers to study TREM2 blockade in vivo without depleting cells or triggering Fc-mediated responses.

• TREM2’s biological relevance:

  • In Alzheimer’s Disease, TREM2 activation in microglia initiates a signaling loop that sustains myeloid cell responses and contributes to disease progression.
  • TREM2 defects cause PLOSL (Nasu-Hakola disease), marked by early-onset dementia and bone pathology.
  • In cancer, TREM2 knockout (or blockade) in mice enhances resistance to tumor growth and improves responsiveness to anti-PD1 immunotherapy, prompting interest in TREM2 as an immunotherapy target.

• Clone 178 (LALAPG) has been widely used in recent studies to dissect the role of TREM2-positive myeloid cells (including tumor-infiltrating macrophages and microglia) in the tumor microenvironment and neurodegeneration. For example, blockade with this antibody is used to understand how TREM2 impacts immune cell subsets and anti-tumor immune responses, especially in combination therapy (e.g., checkpoint inhibitors).

• Recent research using clone 178 (LALAPG):

  • Studies in melanoma and other tumor models used clone 178 (LALAPG) to block TREM2 non-depletively, revealing that TREM2 inhibition can cooperate with cancer vaccines or checkpoint blockade to remodel the tumor microenvironment and promote CD8+ T cell-mediated anti-tumor responses.
  • Single-cell RNA-seq analyses from treated tumors illustrate that blocking TREM2 reshapes immune cell populations within tumors, supporting combination immunotherapy approaches.
  • Cited landmark studies include Deczkowska et al. (2020, Cell), Molgora et al. (2020, Cell), and Keshari et al. (2024, Cell Reports), which explore both neurodegeneration and cancer immunology contexts for TREM2 targeting.

Summary of main mechanistic insights:

• Clone 178 (LALAPG) enables specific, non-depleting functional TREM2 blockade in mice.
• This approach has been critical in demonstrating that TREM2+ myeloid cells can suppress anti-tumor immunity, and that blocking TREM2 enhances responses to immunotherapies.
• The antibody has also clarified the distinct roles of TREM2 in microglia, macrophages, osteoclasts, and other myeloid cells across multiple diseases.

Overall, clone 178 (LALAPG) is a key reagent supporting current mechanistic and translational studies targeting TREM2 in both neurodegeneration and cancer immunotherapy.

Dosing regimens for clone 178 (LALAPG anti-mouse TREM2 antibody) in mouse models typically range from 250??g per injection administered intraperitoneally, but exact protocols may vary depending on the specific disease model and study design.

Clone 178 (LALAPG) is primarily used to block TREM2 function in murine studies of neurodegeneration (such as Alzheimer's Disease), cancer immunotherapy, and other pathologies involving myeloid cells. The antibody is engineered to be Fc-muted, minimizing effector function (antibody-dependent cellular cytotoxicity and phagocytosis).

Key regimen details (based on current literature and manufacturer guidance):

• Dose per injection: Most published studies report administering 250??g per mouse per injection when assessing disease-modifying effects or immunotherapy enhancement.
• Frequency: Injection schedules typically align with standard antibody dosing in mice (e.g., every 3–4 days, or as dictated by the progression of disease or experimental endpoint). However, specific timing for clone 178 (LALAPG) should be confirmed for each protocol, as the literature primarily discusses dosage but less so interval.
• Route: Intraperitoneal (IP) injection is most common and recommended for monoclonal antibodies in preclinical mouse studies.

Comparative context with other checkpoint antibodies:| Antibody | Typical Dose (per mouse) | Frequency | Route ||----------------------|-------------------------|---------------------|------------|| 178 (LALAPG) (TREM2) | 250??g | every 3–4 days* | IP || Anti-PD-1 (RMP1-14) | 200–500??g | every 3–4 days | IP || Anti-PD-L1 | 100–250??g | 2–3 times/week | IP || Anti-CTLA-4 | 100–250??g | every ~3 days | IP |

*Denotes inferred standard scheduling; published protocols for 178 (LALAPG) may adjust based on experimental needs.

Variation between mouse models: While the dose for clone 178 (LALAPG) tends to be consistent at 250??g per injection, experimental models examining neuroinflammation, cancer, or metabolic disease may adapt the regimen frequency or duration to the kinetics of the disease process or outcome measures. In Alzheimer’s models, the antibody is used to modulate microglial activity over several weeks; in tumor studies, regimens parallel those of standard checkpoint inhibitors, which can involve more intensive or prolonged administration.

There is limited public information specifying exact dosing variations across diverse mouse models for clone 178 (LALAPG). Most references report generic dosing suitable for preclinical optimization. For precise regimens in your model of interest, it is recommended to review published protocols specific to that disease context or contact antibody suppliers for pilot data.

Key takeaway:
The standard dosing regimen for clone 178 (LALAPG) in mice is 250??g per injection, administered intraperitoneally every 3–4 days, with potential adjustments based on the mouse model and experimental objectives.