ADC Development for ALCL

Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the ability to deliver highly toxic chemotherapeutic agents that cannot be administered systemically. Currently, ADCs has emerged as an important therapy in cancer treatment. Creative Biolabs is one of the best service providers in the ADC design and development, and we offer a full range of customized ADC development services for Anaplastic large cell lymphoma (ALCL) treatment.

Introduction of ALCL

ALCL is a rare type of non-Hodgkin lymphoma (NHL), and one of the subtypes of T cell lymphoma. ALCL attributes to a translocation of the anaplastic lymphoma kinase (ALK) gene and the nucleophosmin (NPM) gene that formed a novel chimeric fusion protein, NPM-ALK. In the World Health Organization (WHO) classification, ALCL was divided into two types, including the primary cutaneous ALCL (PCALCL) and systemic ALCL. In 2008, systemic ALCL was officially separated into ALK1+ ALCL and ALK-negative (ALK-) ALCL. ALK+ ALCL responds well to standard chemotherapy treatments, providing most patients with long-term remission. By contrast, most patients with ALK-negative ALCL are more likely to relapse within five years. ALK+ ALCL generally arises in children and young adults, while ALK-negative ALCL is more common in patients over the age of 55 years.

Hematoxylin and eosin (H&E) and immunohistochemical staining of ALCL. (Hapgood, 2015) Fig.1 Hematoxylin and eosin (H&E) and immunohistochemical staining of ALCL. (Hapgood, 2015)

ADC Development for ALCL

ADCs are showing obvious advantages and promising in the treatment of ALCL. For example, Brentuximab vedotin (SGN-35) is an ADC specifically targeting ALCL, which consisted of an anti-CD30 antibody conjugated to a potent toxic microtubule-disrupting agent monomethyl auristatin E (MMAE). Brentuximab vedotin harbors the ability to target CD30-positive tumor cells and, it is internalized and MMAE can be released to induce cell cycle arrest and apoptosis upon it bound to CD30. In phase II trials, 86% of patients with refractory or relapsed systemic ALCL presented objective response, with an acceptable toxicity profile. Based on these results, in 2011, brentuximab vedotin has obtained accelerated approval for the treatment of refractory and relapsed HL and ALCL.

Another example is anti-CD30-LDM, which is a novel ADC composing of the intact anti-CD30 monoclonal antibody and Lidamycin (LDM). LDM is a member of the enediyne antibiotic family, which is one of the most potent antitumor agents. The anti-CD30-LDM ADC showed highly cytotoxic to HL (Hodgkin lymphoma) and ALCL cell lines and can significantly induce cell apoptosis and G2/M cell cycle arrest with no discernible adverse effects. Therefore, this ADC shows attractive tumor-targeting capability and antitumor efficacy and could be a promising candidate for the treatment of ALCL.

According to these previous studies, Creative Biolabs’s ADCs development services mainly target the CD30 antigen that is overexpression in the lymphoma cells.

Brentuximab vedotin structure and internalization process. Fig.2 Brentuximab vedotin structure and internalization process. (Katz, 2011)

Target of ADC development for ALCL:

CD30

What Can We Do for You?

With novel technology platform and professional experiment services, Creative Biolabs offers comprehensive ADCs design and development services for the ALCL disease. Based on the commitment of prompt communication and on-time reporting, our staffs will ensure a high-efficiency service to meet the strict project timelines. Please contact us for more details.

References

  1. Hapgood, G.; Savage, K. J. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015, 126(1): 17-25.
  2. Katz, J.; et al. Brentuximab vedotin (SGN-35). Clinical Cancer Research. 2011, 17(20): 6428-6436.


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