Anti-Mouse CTLA-4 (CD152) [Clone UC10-4F10-11] — Purified in vivo GOLD™ Functional Grade

Clone UC10-4F10-11 is most commonly used in mice for in vivo blockade of CTLA-4 (CD152) to study immune checkpoint inhibition, promote T cell activation, and investigate mechanisms of anti-tumor immunity or immune tolerance.

Key in vivo applications include:

• Immuno-oncology studies: Blocking CTLA-4 with UC10-4F10-11 augments T cell co-stimulation by preventing CTLA-4 from engaging B7 ligands (CD80/CD86), thereby promoting CD28-mediated activation and anti-tumor responses in cancer models.
• Immunotherapy research: The antibody is used to test experimental cancer immunotherapies, both as monotherapy and in combination with other immune checkpoint inhibitors or cancer vaccines, to dissect mechanisms of response and resistance.
• Tolerance and autoimmunity models: Researchers employ UC10-4F10-11 in tolerance induction studies, transplant rejection models, and autoimmune disease models to study loss of regulatory CTLA-4 signaling and its impacts on immune activation.
• Functional immune pathway analysis: The antibody is used to define CTLA-4's role in the regulation of T cell activation, peripheral tolerance, and immune homeostasis in vivo.
• Hematopoietic stem cell transplantation and tumor challenges: In some protocols, UC10-4F10-11 is administered after bone marrow transplantation and tumor inoculation to study effects on tumor growth, survival, and immune system reconstitution.

Additional notes:

• UC10-4F10-11 is available in low-endotoxin "in vivo grade" formulations suitable for mouse studies.
• Its main mechanism is neutralization of CTLA-4, not depletion of CTLA-4-expressing cells.
• Commonly tested endpoints include tumor growth, T cell activation status, immune infiltrate analysis, and survival.
• Aside from in vivo use, UC10-4F10-11 is also validated for flow cytometry, ELISA, and Western blot (mainly for in vitro applications).

In summary, UC10-4F10-11 is a standard tool for in vivo blockade of CTLA-4 to probe immune regulation, especially in cancer immunology and tolerance models in mice.

Commonly used antibodies or proteins with UC10-4F10-11 (anti-mouse CTLA-4) in immunology literature typically include:

• Other anti-CTLA-4 clones such as 9H10 and 9D9, often used for comparison or validation of results.
• Isotype controls, especially Armenian hamster IgG, to control for non-specific binding in experiments using hamster-derived UC10-4F10-11.
• Anti-CD28 antibodies, due to the functional interplay between CD28 and CTLA-4 in T cell co-stimulation and inhibition.
• T cell phenotyping antibodies, such as anti-CD3 (clone 145-2C11), and often anti-CD4, anti-CD8, and other lineage or activation markers, to characterize T cell responses .
• Tumor immunity studies frequently pair UC10-4F10-11 with antibodies to immune checkpoint molecules (e.g., anti-PD-1, anti-PD-L1) or immunoregulatory cytokines, depending on study focus.
• Control antibodies, such as irrelevant hamster or rat IgGs (e.g., PARSI 19 for hamster IgG1 or Lo-DNP for rat IgG2b) to rule out non-specific Fc-mediated effects.

Context and application often dictate which of these are prioritized. For example:

• Flow cytometry panels may include anti-CD152 (CTLA-4, UC10-4F10-11) together with anti-CD3, anti-CD4, anti-CD8, and other functional or activation markers.
• In vivo blockade or depletion studies will almost always use isotype controls and sometimes the alternative anti-CTLA-4 clones to confirm specificity.

Summary Table: Common Co-Used Antibodies/Proteins with UC10-4F10-11

These combinations are routinely described in immunology and cancer research, and the exact panel is determined by the experimental goals.

Key findings from the use of clone UC10-4F10-11 in scientific literature primarily focus on its role in blocking CTLA-4 (Cytotoxic T-Lymphocyte-Associated protein 4) in mice. Here are some key points:

1. Functionality: Clone UC10-4F10-11 is a monoclonal antibody that blocks CTLA-4, preventing it from binding to B7 co-receptors. This blockade allows for enhanced CD28 binding, thereby promoting T cell co-stimulation.

2. Application: It is commonly used in in vivo mouse studies to neutralize CTLA-4, which is a crucial immune checkpoint molecule involved in regulating T cell responses.

3. Comparison with Other CTLA-4 Antibodies: Unlike some other anti-CTLA-4 antibodies (e.g., clone 9H10), UC10-4F10-11 does not induce significant Treg depletion via antibody-dependent cellular cytotoxicity (ADCC).

4. Impact on Tumor Response: Studies have shown that anti-CTLA-4 treatments generally enhance antitumor responses by promoting immune cell activity. However, the effectiveness can vary depending on the specific antibody used, with some clones like UC10-4F10-11 showing less robust tumor control compared to others.

5. T Cell Activation and Memory Response: Anti-CTLA-4 treatments, including those using UC10-4F10-11, have been observed to generate robust memory T cell responses, which are crucial for long-term antitumor immunity.

Overall, clone UC10-4F10-11 is a valuable tool for studying CTLA-4's role in immune regulation and its potential in cancer therapy by enhancing T cell activation and antitumor responses.

Dosing regimens of clone UC10-4F10-11 vary across different mouse models based on the experimental context, disease model, and specific research objectives. The general recommended range for in vivo studies is 50–250 µg per mouse per administration, though the precise dosing depends on several factors.

Common Dosing Protocols

The most frequently employed dosing regimen is 100 µg per mouse, administered intraperitoneally. This dose has been used successfully in multiple experimental contexts, including tumor models and immunization studies. However, the dosing frequency and duration vary significantly depending on the experimental design.

Tumor Models

In cancer immunotherapy studies, the timing and frequency of administration are particularly important. For B16 melanoma models, the antibody was given on days 4, 7, and 10 post-tumor inoculation at 100 µg per dose. This three-dose regimen initiated shortly after tumor establishment has proven effective for inducing tumor rejection when used alone or in combination with other checkpoint inhibitors.

Some studies have utilized a different approach with 20 mg/kg dosing, which translates to approximately 400-500 µg for a standard mouse weighing 20-25g. This higher dose demonstrates the flexibility in dosing strategies depending on the therapeutic goals and tumor type being studied.

Immunization and Priming Studies

When used to modulate immune responses during T cell priming, the antibody is typically administered at 100 µg on consecutive days during the peak of T cell activation. For example, in keyhole limpet hemocyanin (KLH) immunization models, UC10-4F10-11 was given on days 3, 4, and 5 following initial immunization. This timing coincides with the upregulation of CTLA-4 expression on activated CD4+ T cells, allowing the antibody to effectively modulate the immune response during the critical priming phase.

Factors Influencing Dosing Decisions

The variation in dosing regimens reflects differences in mouse strain susceptibility, the kinetics of the disease model, and whether the antibody is used as monotherapy or in combination with other agents. When combined with other checkpoint inhibitors like anti-PD-L1, the dosing schedule must be coordinated to achieve optimal synergy, often resulting in staggered administration patterns.