Anti-Mouse CD152 (CTLA-4) [Clone 9H10] — Purified in vivo PLATINUM™ Functional Grade

Clone 9H10 is commonly used in vivo in mice to block CTLA-4 (CD152), thereby enhancing T cell activation and augmenting anti-tumor immune responses.

Key in vivo applications include:

• Immune checkpoint blockade in cancer models: 9H10 is widely employed in preclinical cancer immunotherapy to inhibit CTLA-4, allowing co-stimulatory signaling via CD28 and boosting anti-tumor T cell activity. This application is central to studies of immune-mediated tumor rejection, particularly in syngeneic models like CT26 colon carcinoma and B16 melanoma.
• Depletion of intra-tumoral regulatory T cells (Tregs): Several studies show that 9H10 can deplete Tregs within the tumor microenvironment, which further enhances tumor-specific immunity by reducing local immunosuppression.
• Study of T cell regulation and tolerance: By neutralizing CTLA-4, 9H10 has been utilized to investigate mechanisms governing T cell activation, autoimmunity, and tolerance in various immunological settings, including disease and transplantation models.
• Combination therapy research: 9H10 is often used in combination with other immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) or with conventional therapies to model and optimize multi-agent immunotherapy regimens in vivo.

All these applications depend on the antibody’s ability to block the interaction between CTLA-4 and its ligands (CD80/CD86), thereby modulating T cell responses for research into cancer, autoimmunity, and immune regulation.

In summary: The most common in vivo use of clone 9H10 in mice is to functionally block CTLA-4 for cancer immunotherapy modeling, Treg modulation, and study of T cell-mediated immune responses.

Commonly used antibodies or proteins alongside 9H10 (anti-CTLA-4) in the literature include antibodies targeting CD28, B7 family members (CD80/CD86), and other checkpoint inhibitors such as anti-PD-1 or anti-PD-L1. Additionally, other anti-CTLA-4 antibody clones—such as 9D9, UC10-4F10, and 4F10—are frequently used in similar experimental contexts.

Key proteins and antibodies used in conjunction with 9H10:

• CD28: Frequently studied because blocking CTLA-4 with 9H10 enhances CD28-mediated T cell co-stimulation, as these molecules compete for binding to CD80/CD86.
• B7 family (CD80/CD86): The ligands for CTLA-4 and CD28; manipulation or detection of these molecules is common in studies assessing immune checkpoint blockade.
• Other anti-CTLA-4 clones: Includes 9D9, UC10-4F10, and 4F10, which are used to compare efficacy or mechanisms of CTLA-4 blockade in immunotherapy models.
• Checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1): Combination therapies involving CTLA-4 and PD-1 or PD-L1 blockade are widely investigated in cancer immunotherapy, although specific details about their concomitant use with 9H10 may depend on experimental design.
• Regulatory T cell markers: Antibodies for FoxP3 and related Treg markers are often used in mechanistic studies involving CTLA-4 blockade to evaluate immune modulation in the tumor microenvironment.

Alternative context: If referring to the 9H10 antibody against influenza hemagglutinin, other stalk-targeting broadly neutralizing antibodies, such as CR8020 and CR8043, are often used for comparative binding and functional studies.

For most research applications involving CTLA-4 (the canonical 9H10 clone), combinations typically feature:

• CD28 (functionally relevant)
• B7 family proteins
• Other checkpoint inhibitors
• Alternate anti-CTLA-4 clones for validation or mechanistic comparison

These combinations enable exploration of immune activation, checkpoint pathways, and potential synergies in immunotherapy.

The clone 9H10, an anti-CTLA-4 antibody, has been extensively studied in scientific literature for its role in immunotherapy, particularly in cancer research. Here are some key findings from citations involving clone 9H10:

1. Selective Depletion of Intra-tumoral Tregs:

   • Clone 9H10 selectively depletes intra-tumoral regulatory T cells (Tregs) without affecting those in the spleen or lymph nodes, which is crucial for enhancing antitumor responses.
   • This selective depletion is attributed to its ability to induce antibody-dependent cellular cytotoxicity (ADCC), which is facilitated by its binding to Fcγ receptors.

2. Promotion of T Cell Activation:

   • By blocking CTLA-4, clone 9H10 promotes T cell activation by preventing CTLA-4 from binding to B7 co-receptors (CD80 and CD86), allowing CD28 to bind instead, which is essential for co-stimulation of T cells.

3. Comparison with Other Antibodies:

   • Clone 9H10 has been compared with other anti-CTLA-4 antibodies (like 9D9 and UC10-4F10) and anti-PD-1 antibodies. It has shown superior effects in some studies, particularly in terms of Treg depletion and inducing a robust memory antitumor response.
   • While anti-PD-1 antibodies do not support ADCC for Treg depletion, clone 9H10's effectiveness is also linked to its intrinsic effects on T cells rather than just Treg depletion.

4. In Vivo Efficacy in Cancer Models:

   • Clone 9H10 has demonstrated efficacy in various cancer models, including melanoma, where it has shown minimal tumor growth in treated mice upon rechallenge, indicating its potential in enhancing long-term antitumor immunity.

5. Mechanism of Action:

   • Its high affinity for FcγRIV suggests a significant role in the depletion of tumor-infiltrating Tregs through ADCC, which is a key component of its mechanism of action.

Overall, clone 9H10 is valued for its ability to selectively deplete intra-tumoral Tregs, promote T cell activation, and enhance antitumor responses, making it a potent tool in cancer immunotherapy research.

Dosing regimens of clone 9H10 (anti-CTLA-4) in mouse models show considerable variation depending on the specific tumor model, experimental goal, and administration route, but most commonly involve 100–200 μg per mouse given intraperitoneally every 3 days. Some protocols use different dose levels, routes, or frequencies based on therapeutic and toxicity considerations.

Key dosing approaches include:

• Standard Immunotherapy in Syngeneic Tumor Models:

  • 100–200 μg per mouse, intraperitoneally, every 3 days is the most widely reported regimen for CTLA-4 blockade in cancer immunotherapy models.
  • This regimen is used in various tumor models, often either as monotherapy or in combination with other checkpoint inhibitors.

• Alternative Dose Ranges and Schedules:

  • Intravenous administration: Studies employ dose titrations ranging from 0.625 to 10 mg/kg intravenously every 3 days for three doses, particularly when examining dose-response or pharmacological modeling.
  • Lower-dose regimens: Some studies, particularly when using combination therapies or targeting toxicity, have successfully employed lower doses (e.g., 10–30 μg per mouse per injection), given biweekly or every 3 days, sometimes via intratumoral injection.
  • Step-down regimens: In certain protocols, a higher initial dose (e.g., 200 μg) is followed by lower subsequent doses (e.g., 100 μg), providing robust activation while minimizing toxicities.

• Combination Therapy and Experimental Modifications:

  • In combination with other checkpoint inhibitors (such as anti-PD-1), dosing generally mirrors the single-agent regimen but may be adjusted to mitigate synergistic toxicity or optimize efficacy.

• Model-Specific Variation:

  • Dosing can be tailored for specific tumor models, immunological context, or experimental endpoints. For example, MC38 (colon adenocarcinoma), A20 (lymphoma), and B16 (melanoma) models may have slight titrations depending on sensitivity, tumor burden, and study design.

Summary Table—Representative Dosing Regimens for Clone 9H10 in Mouse Models:

These regimens are frequently adapted based on experimental considerations, observed toxicities, and specific aims (e.g., monotherapy, combination therapy, immune memory studies). Always reference published protocols particular to the tumor model and research objective for precise implementation.