ADC Development Services Targeting CD25

As a class of novel cancer therapeutics with antigen specificity and potent cytotoxicity, Antibody-drug conjugates (ADCs) are developed actively. Creative Biolabs provides a full range of ADC construction services from antibody discovery and drug production to ADC conjugation. In addition, we have innovative linker and linker-payload technologies to improve the homogeneity, PK/PD and efficacy of ADC drugs. We are confident to boost your ADC development with our experienced scientists and state-of-the-art facilities.

Introduction of CD25

CD25, also known as interleukin-2 receptor alpha chain (IL-2R1), is encoded by the IL2RA gene in human. It is a 55 kDa single-chain transmembrane glycoprotein. The receptor can interact with IL-2 (IL-2Ra) with low affinity, while it can produce a high-affinity IL-2R complex after combining with p75 beta-chain (CD122 antigen, IL-2Rb). CD25 mainly presents on activated T and B cells, activated macrophages, T cell clones and NK cells. As a receptor, it plays a critical role in recognizing the HTLV-1, and it is also an important marker used in identified CD4⁺FoxP3⁺ regulatory T cells in mice. It is a marker of memory T cells and lymphoma cells in human. Thus, CD25 is a target used in cancer treatment such as the Hodgkin lymphoma and non-Hodgkin lymphoma (NHL).

Fig.1 Pathways of activation of naïve CD4⁺CD25⁺ T regulatory cell (Treg) (tTreg). (Hall, 2017)

Anti-CD25 ADC for Lymphoma

Compared to conventional medicines' poor outcomes for the treatment of refractory lymphomas, ADCs are becoming potential and promising therapeutic agents. CD25 is overexpressed on many lymphoma cells such as the HL and NHL, which is regarded as a target in ADCs development.

For example, ADCT-301 is an ADC composed of an anti-CD25 human IgG1 antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer payload via a dipeptide cleavable linker. Pre-clinical trials showed that ADCT-301 presents high affinity and has highly potent and selective cytotoxicity against CD25-expressing human lymphoma cell lines. Generally, once bound with CD25 and internalized, drug can be released and perform its potent cytotoxic action through interacting with DNA, then resulting in apoptosis of tumor cells. ADCT-301 also can kill CD25-negative cells by the bystander effect. A dose-dependent and targeted antitumor activity against CD25-positive lymphoma also has been observed in the in vivo studies. All together, ADC against CD25 is a promising therapeutic agent in treating CD25-expressing lymphoma.

Fig.2 ADCT-301 is an ADC composed of a human IgG1, HuMax®-TAC against human IL-2R-α (CD25) conjugated through a cleavable linker to a PBD dimer warhead with a drug-antibody ratio of 2.3 ± 0.3. (Flynn, 2015)

What Can We Do for You?

Creative Biolabs has long-term devoted to the development of ADCs and we have finished lots of projects based on our extensive experience. Creative Biolabs is confident in offering the best ADCs services and products targeting CD25 for our customers all over the world. If you are interested in our service, please do not hesitate to contact us for more details.

Our ADCs development services including but not limited to:

• ADC Antibody Screening
• DrugLnk™ Custom Synthesis
• Antibody Design and Conjugation
• ADC in vitro Analysis
• ADC in vivo Analysis

References

1. Hall, B. M.; et al. Changes in Reactivity In Vitro of CD4⁺ CD25⁺ and CD4⁺ CD25-T Cell Subsets in Transplant Tolerance. Frontiers in immunology. 2017, 8: 994.
2. Flynn, M. J.; et al. Mechanistic and pharmacodynamic studies of adct-301, a pyrrolobenzodiazepine (PBD) dimer-containing antibody drug conjugate (ADC) targeting CD25-expressing hematological malignancies. 2015.

For Research Use Only. NOT FOR CLINICAL USE.