ADC Development Services Targeting CD123

Antibody-drug conjugate (ADC) is a type of novel and effective therapy for cancers. This approach is displaying significant advantages including the improved potency and decreased toxic side effects through targeted delivering toxin to tumor cells by monoclonal antibody. Creative Biolabs is committed to ADC design and development for many years, and now offers a comprehensive set of ADC preparation services against CD123 for your cancer research.

Introduction of CD123

CD123, also known as IL3R alpha, is a protein expressed on the cells to facilitate the transmission of interleukin-3 signal in the immune system. It generally presents as a complex with the IL-3R beta chain. CD123 is encoded by the CD123 gene located in the Pseudoautosomal Region (PAR) at the end of the short arm of the X and Y chromosome. It is widely expressed in leukemic blast cells in various hematologic malignancies such as acute myeloid and B-lymphoid leukemia, Blastic Plasmocytoid Dendritic Neoplasms (BPDCN) and hairy cell leukemia, while low or absent on normal hematopoietic stem cells. Thus, CD123 represents a potentially important target for the development of new therapeutic agents for leukemia.

Fig.1 Bispecific mechanism recruits cytotoxic T cells to kill AML stem cells & blasts. (Chu, 2014)

Anti-CD123 ADC in Acute Myeloid Leukemia (AML)

SGN-CD123A is a novel ADC targeting the CD123 for the AML treatment, which is composed of a humanized anti-CD123 antibody conjugated to a highly potent DNA binding pyrrolobenzodiazepine (PBD) dimer drug through a protease-cleavable dipeptide linker. In this ADC, the antibody with two engineered cysteines is linked to two PBD dimers. Preclinical studies showed that SGN-CD123A can be internalized rapidly and release the drug within lysosomes to cause the death of CD123-positive AML cells. It is reported that SGN-CD123A presented significant antitumor activity in AML xenograft models. Currently, SGN-CD123A is investigated in phase I trial. To date, all of these positive data in preclinical models demonstrated that SGN-CD123A may represent a promising new approach for the treatment of AML.

Fig.2 Chemical structure of SGN-CD123A, comprised of the monoclonal antibody h7G3ec and drug linker (SGD-1910). (Li, 2018)

What Can We Do for You?

Treatment choices for AML patients resistant to conventional chemotherapies are limited, novel and more effective therapies are needed. CD123 is expressed on the majority of AML blasts but low or lack in normal cells, which makes it an attractive and potential target for AML treatment. Equipped with state-of-the-art research and manufacturing facilities, Creative Biolabs is dedicated to helping our clients design and prepare highly customized ADCs targeting CD123. With the novel technology platforms and professional scientist team, Creative Biolabs is capable of offering you the best ADCs services. Please feel free to contact us for more details.

Our ADCs 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. Chu, S. Y.; et al. Immunotherapy with long-lived anti-CD123×anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human AML cell lines and of CD123+ cells in monkeys: a potential therapy for acute myelogenous leukemia. 2014.
2. Li, F.; et al. Characterization of SGN-CD123A, a potent CD123-directed antibody-drug conjugate for acute myeloid leukemia. Molecular cancer therapeutics. 2018, 17(2): 554-564.

For Research Use Only. NOT FOR CLINICAL USE.