ADC Development for CLL

Chronic lymphocytic leukaemia (CLL) is one of the most common types of leukaemia. Although conventional therapy have been highly successful of patients with the CLL, most still relapse. Current CLL therapy is already associated with significant toxicities, limiting further intensification of therapy. Thus, novel therapies such as antibody-drug conjugates (ADCs) are developing rapidly. With more than 10 years of experience in antibody preparation and bio-conjugation chemistry, Creative Biolabs now provides customers with comprehensive ADC development services for CLL. With combined expertise in chemistry, immunology, and molecular biology, our scientific team can help you with every step of the ADC development process, from design to validation.

Introduction of CLL

CLL is a type of cancer of the blood and bone marrow, where the bone marrow produces too many lymphocytes. This disease most commonly arises in people over the age of 50, and males are affected more often than females. Generally, there is no typically symptom in the early stage, while later symptoms include non-painful lymph nodes swelling, fatigue, fever, night sweats, weight loss, frequent infections and pain of the abdomen caused by an enlarged spleen. These symptoms will worsen gradually. It is reported that risk factors of CLL include exposure to chemicals, family history of blood and bone marrow cancers. Moreover, CLL causes the buildup of immature B cell lymphocytes in the bone marrow, lymph nodes, and blood, and these abnormal cells can crowd out healthy blood cells. CLL is divided into two main types based on with or without mutated IGHV gene. Treatments for CLL include chemotherapy or immunotherapy upon significant symptoms appeared.

Chronic lymphocytic leukaemia (CLL). Fig.1 Chronic lymphocytic leukaemia (CLL).

ADC Development for CLL

The treatment landscape for patients with CLL has changed considerably with the introduction of very effective targeted therapies including the ADC therapy. CD74 is an attractive target associated with hematologic tumors, and it is also expressed in solid cancers. IMMU‑115 is an ADC that is directed against CD74, the ADC contains a pH‑sensitive linker, which allows rapid release of the drug once the ADC enters the acidic environment of the tumour cell. The ADC is currently being investigated in phase II trials in CLL and NHL.

Structure of milatuzumab-doxorubicin (anti-CD74). Fig.2 Structure of IMMU‑115. (Nanna, 2017)

In addition, CD37 is expressed on B cells and severs as another therapeutic target in CLL. IMGN529 is an ADC against the CD37, composed of an anti-CD37 antibody conjugated to the maytansinoid, DM1, a potent antimicrotubule agent, via the thioether linker. IMGN529 maintains the intrinsic antibody activities and demonstrates enhanced cytotoxic activity from targeted payload delivery. Phase 1 clinical trials indicated that IMGN529 resulted in potent and specific depletion of CLL B cells. These results support evaluation of the CD37-targeted ADC in clinical trials in patients with B-cell malignancies including NHL and CLL.

Our ADC development services for CLL include but not limited to:

CD22     CD74

What Can We Do for You?

ADCs have emerged over the last decade as one of the most promising new therapy for the selective ablation of tumor cells. As a pioneer company of ADC development, Creative Biolabs has developed extensive platforms for antibody production and linker-payload preparation to provide our customers with high-quality ADC development service for CLL treatment. Our professional scientists will work closely with you to boost your cancer research. If you are interested in our services, please contact us for more information.

Reference

  1. Nanna, A. R.; et al. Chemical Assembly of Antibody-Drug Conjugates. Next Generation Antibody Drug Conjugates (ADCs) and Immunotoxins. Springer, Cham, 2017: 1-28.

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