Anti-Mouse CD137 (4-1BB) [Clone 3H3] — Purified in vivo GOLD™ Functional Grade

Clone 3H3 is a well-characterized agonistic monoclonal antibody targeting mouse CD137 (4-1BB). It is widely used in in vivo mouse studies for several applications:

1. Immune Modulation: Clone 3H3 stimulates the 4-1BB co-stimulatory receptor, enhancing T-cell-mediated proliferative responses and cytokine production, which is beneficial for immune modulation.

2. Cancer Research: The antibody is used to investigate its potential in cancer immunotherapy by enhancing antitumor immunity. It promotes the proliferation and survival of T cells, increasing their cytolytic activity against tumor cells.

3. Infectious Disease Models: Clone 3H3 can be used to study the role of immune responses in infectious diseases, leveraging its ability to modulate immune cell activity.

4. Functional Assays: Beyond direct in vivo applications, clone 3H3 is also utilized in ELISA, flow cytometry, and other functional assays to study biological pathways affected by the 4-1BB protein.

Overall, clone 3H3 is a valuable tool for studying immune responses and developing immunotherapeutic strategies.

Commonly used antibodies and proteins studied with 3H3 (an agonistic anti-4-1BB/CD137 antibody) in the literature include other co-stimulatory and checkpoint pathway markers such as anti-PD-1, anti-TIGIT, the anti-4-1BB antibody LOB12.3, and cellular markers for immune profiling like CD25, NK1.1, CD44, CD49b, CD62L, CD8β, CD3ε, CD4, Gr-1, and OX40.

Key examples from published studies:

• Checkpoint inhibitors: Frequently, 3H3 is combined with anti-PD-1, anti-PD-L1, and anti-CTLA-4 in immunotherapy research to evaluate synergistic or combinatorial effects on tumor immunity.
• Other anti-4-1BB antibodies: The LOB12.3 clone is often used for comparative studies to analyze differences in co-stimulatory activity and tissue toxicity between anti-4-1BB agents.
• Immune exhaustion and activation markers: Analysis often includes markers like PD-1 and TIGIT, useful for identifying exhausted T cell populations following 3H3 treatment.
• Flow cytometry immune profiling: Studies commonly utilize a broad panel of antibodies against surface markers such as CD25, NK1.1, CD44, CD49b, CD62L, CD8, CD3, CD4, Gr-1, OX40, and MHC class II to characterize T cells, NK cells, dendritic cells, and myeloid populations in response to 3H3 administration.
• Galectin family and related proteins: Antibodies against Galectin-9 (Gal-9) and Galectin-3 (Gal-3) are sometimes used to investigate regulatory mechanisms in 4-1BB–mediated immune responses.

Summary table of commonly co-used antibodies/proteins with 3H3:

Most commonly, the focus is on checkpoint inhibitors, co-stimulatory agonists, and comprehensive immune profiling panels when 3H3 is used to dissect immune responses in the context of cancer immunotherapy or T cell biology.

Clone 3H3, an antibody targeting CD137 (4-1BB), has been widely studied in scientific literature, particularly in the context of cancer immunotherapy. Here are the key findings from its citations:

1. Agonistic Activity on CD137: Clone 3H3 is a strong agonist of mouse CD137, known for inducing significant T-cell activation and proliferation. It causes substantial changes in the peripheral immune system, including the expansion of liver CD8+ T cells and an increase in PD1+/TIGIT+ T cells in the spleens and livers of treated mice.

2. Hepatic Inflammation: The use of clone 3H3 has been associated with hepatic inflammation, which is a notable side effect in some studies.

3. Comparison with Other Agonists: In comparison to other CD137 agonists like CTX-471, clone 3H3 demonstrates broader T-cell activation but may have a narrower therapeutic window due to its stronger agonistic effects.

4. Role in Tumor Models: Clone 3H3 is commonly used in mouse tumor models to enhance peripheral immune activation, which is influenced by factors such as mouse strain and dosing regimen.

5. Immune Cell Costimulation: Clone 3H3 has also been shown to costimulate mast cells, enhancing IgE + Ag-induced cytokine production.

These findings highlight the potential of clone 3H3 in cancer immunotherapy by augmenting immune responses, although its use must be balanced with potential inflammatory side effects.

Dosing regimens of clone 3H3, an agonistic anti-mouse CD137 (4-1BB) antibody, vary considerably across different mouse models based on factors such as mouse strain, disease type, experimental goal, and isotype version.

Essential context and details:

• Typical Doses in Tumor Models: 3H3 is used at doses sufficient to activate peripheral immune responses, commonly ranging from 50 to 200 μg/mouse per injection. Dosing may be adjusted for the aggressiveness of the tumor or immune evasion characteristics.
• Route of Administration: Most studies administer 3H3 intraperitoneally (i.p.), though intravenous (i.v.) delivery is sometimes used.
• Dosing Frequency: The standard regimen involves dosing once weekly or every 3–4 days for several consecutive weeks, often 2–4 doses per experimental cycle. Variations exist, especially in combination protocols.
• Isotype and Strain Dependence: The immune activation elicited by 3H3 can differ with the isotype used (e.g., rat IgG2a vs. mouse IgG) and the mouse strain (such as C57BL/6 vs. BALB/c), influencing dosing adjustments for optimal efficacy. For example, some strains may exhibit stronger peripheral T cell expansion at lower doses.
• Combination Studies: 3H3 is frequently used in combination with other immunomodulatory antibodies, and regimens are tailored to minimize toxicity while maximizing synergistic effects; this can lead to protocol-specific dosing variations.

Additional relevant information:

• Peripheral Immune Activation: Studies have shown that 3H3 dosing results in robust peripheral activation—such as expanded CD8+ populations and increased PD-1+TIGIT+ T cells in the spleen and liver—which informs both dose selection and frequency adjustments.
• Experimental Context: In autoimmune disease models or memory B cell studies, dosing can be further reduced to avoid exaggerated immune stimulation, sometimes as low as 50 μg/mouse every 7 days.

In summary, 3H3 dosing regimens range widely (typically 50–200 μg/mouse i.p., given every 3–7 days), with adjustments depending on model, strain, and experimental context. For precise protocols, consulting the original published experimental setup relevant to the disease model is essential, as dose and schedule are often optimized empirically for each study.