Novel CD25 Antibodies: Enhancing Anti-Tumor Immunity via Selective Regulatory T Cell Depletion—A Literature Analysis

1. Literature Information

·       Research Topic: Development and preclinical evaluation of non-blocking CD25 antibodies for selective regulatory T cell (Treg) depletion in cancer immunotherapy

·       Core Finding: Novel non-IL-2-blocking CD25 antibodies (e.g., RG6292) mediate selective Treg depletion via ADCC/ADCP without impairing effector T cell function, remodeling the tumor microenvironment and enhancing anti-tumor immunity

·       Key Tools: CD25/IL-2Rα recombinant rabbit monoclonal antibodies from ANT BIO PTE. LTD.

·       Application Scenarios: Treg identification, tumor immunotherapy research, preclinical efficacy evaluation, and flow cytometry-based immune profiling

2. Research Background

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis and preventing autoimmune diseases. However, in the tumor microenvironment (TME), Tregs suppress effector T cell activation and function, promoting tumor immune escape and worsening patient prognosis. This dual role makes selective Treg modulation a promising direction in cancer immunotherapy.

CD25 (IL-2Rα), highly and specifically expressed on Treg surfaces, is an ideal target for selective depletion. Traditional CD25 antibodies (e.g., Daclizumab) were designed to block IL-2 binding, but this mechanism inhibits both Tregs and effector T cells—limiting their utility in cancer treatment. Additionally, their Fc regions have low affinity for immune effector cells, failing to mediate effective antibody-dependent cell-mediated cytotoxicity (ADCC) for specific Treg depletion. These limitations drove the development of novel CD25 antibodies with improved selectivity and anti-tumor efficacy, supported by high-quality CD25 detection tools from ANT BIO PTE. LTD.

3. Research

1.     Novel Antibody Design: Develop non-IL-2-blocking CD25 antibodies by combining variable regions of non-blocking IgM CD25 antibodies with structures capable of mediating Treg depletion, ensuring high-affinity CD25 binding without interfering with IL-2 signaling.

2.     Mechanism Validation: Verify that the novel antibody mediates ADCC/ADCP via Fcγ receptor binding, selectively depleting Tregs while preserving effector T cell function.

3.     Preclinical Efficacy Evaluation:

o   Cellular Experiments: Assess Treg depletion efficiency, specificity, and impact on effector T cell activation (STAT5 signaling, Granzyme B/Ki67 expression) in vitro.

o   Animal Models: Evaluate Treg depletion in blood, spleen, and tumor tissue of humanized tumor-bearing mice, and measure CD8+ T cell activity and tumor growth inhibition.

4.     Clinical Translation Exploration: Investigate potential monotherapy or combination therapy (with immune checkpoint inhibitors) strategies, and address safety considerations (immune homeostasis, autoimmune side effects).

4. Research Results

4.1 Design and Mechanism of Novel Non-Blocking CD25 Antibodies

·       Innovative Design: The novel antibody (RG6292) binds CD25 with high affinity but does not block IL-2 binding to its receptor, preserving IL-2 signaling.

·       Effector Mechanisms: Mediates efficient ADCC and antibody-dependent cellular phagocytosis (ADCP) by interacting with Fcγ receptors on immune effector cells (e.g., NK cells, macrophages), achieving selective Treg depletion.

4.2 Preclinical Cellular Experiment Results

·       Preserved Effector T Cell Function: Unlike traditional blocking antibodies, RG6292 does not inhibit STAT5 signaling, maintaining normal Granzyme B and Ki67 expression in effector T cells.

·       Selective Treg Depletion: Exhibits concentration-dependent Treg depletion efficiency with minimal impact on CD4+ and CD8+ effector T cells, critical for retaining anti-tumor immune responses.

 4.3 Preclinical Animal Model Results

·       Treg Depletion in Vivo: In humanized tumor-bearing mice, RG6292 treatment leads to dose-dependent Treg reduction in blood, spleen, and tumor tissue—near-complete depletion at 10 mg/kg.

·       Enhanced Anti-Tumor Immunity: CD8+ T cell activity (measured by Granzyme B) is significantly enhanced, coinciding with reduced tumor growth, confirming reversal of Treg-mediated immunosuppression.

5. Product Empowerment

ANT BIO PTE. LTD.’s STARTER brand CD25/IL-2Rα recombinant rabbit monoclonal antibodies played a pivotal role in this research:

1.     Treg Identification and Sorting: Enabled precise detection and isolation of CD4+CD25+Foxp3+ Tregs via flow cytometry, supporting specificity validation of the novel therapeutic antibody.

2.     Mechanism Research: Facilitated quantification of Treg depletion efficiency and effector T cell activation status (CD25 expression) in vitro and in vivo.

3.     Preclinical Efficacy Monitoring: Supported immune profiling of tumor-bearing mice, tracking Treg numbers in multiple tissues and correlating with anti-tumor efficacy.

4.     Core Product Advantages:

o   High Specificity: Accurately recognizes human CD25 without cross-reactivity, ensuring reliable Treg identification.

o   Ready-to-Use Convenience: PBS-only formulation avoids carrier protein interference, enabling direct flow cytometry use and reducing non-specific background.

o   Batch Consistency: Strict quality control ensures stable performance across preclinical experiments, supporting reproducible data.

6 Brand Mission

ANT BIO PTE. LTD. is a leading provider of life science reagents, offering a comprehensive portfolio including antibodies, recombinant proteins, kits, and general laboratory reagents. We operate three specialized sub-brands:

·       Absin: Focuses on general reagents and kits for broad experimental applications.

·       Starter: Specializes in high-quality antibodies, including CD25/IL-2Rα recombinant rabbit monoclonal antibodies—critical for Treg research and immunotherapy development.

·       UA: Concentrates on recombinant proteins for functional studies and drug development.

Guided by the principle of "Empowering Scientific Discovery Through Precision Reagents," we adhere to strict international quality standards (EU 98/79/EC, ISO9001, ISO13485) and advanced development platforms. Our mission is to provide researchers and biopharmaceutical companies worldwide with reliable, high-performance tools and professional technical support, accelerating breakthroughs in cancer immunotherapy, immunology, and translational medicine to advance human health.

7.Related Product List

8.AI Disclaimer

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ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.