ADC Development for AML

Acute myeloid leukemia (AML) is one of the most common acute leukemia in the world. Although a lot of research are aimed at improving the outcomes in AML, the standard therapy for most subtypes of newly diagnosed AML is still unchanged for the past four decades. Currently, Antibody-drug conjugates (ADCs) are showing significant potential in the AML treatment. As a well-recognized leader in ADC development, Creative Biolabs is dedicated to offering comprehensive high-quality ADC design and construction services for our clients.

Introduction of AML

AML is a cancer of the myeloid line of blood cells starting in the bone marrow, characterized by the rapid growth of abnormal cells in the bone marrow and blood affecting normal blood cells. Symptoms often include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. It can spread to other organs of the body including the brain, skin, gums, lymph nodes, liver or spleen. AML is a kind of acute leukemia, which presents rapid progress and is fatal within weeks or months if no treatment. Risk factors for AML include getting older, chemotherapy or radiation therapy, smoking, exposure to certain chemicals and genetic syndrome. The potential mechanism of this cancer involves the replacement of normal bone marrow with leukemia cells, which causes a decrease of the red blood cells, platelets, and normal white blood cells. According to statistics, AML commonly arises in older adults. Its standard therapies include chemotherapy, radiation therapy, or a stem cell transplant and novel immunotherapy, such as ADC, is investigated actively currently.

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. Fig.1 Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow.

ADC Development for AML

ADCs consist of monoclonal antibodies conjugated to various toxins, which are a tool to bridge conventional chemotherapy and innovative immunotherapy. To date, several ADCs have been developed for the AML treatment. CD33 (SIGLEC-3) is an important target in AML, and Gemtuzumab ozogamicin (Mylotarg) is a prominent ADC in clinical application, comprising a humanized anti-CD33 IgG4 antibody conjugated to calicheamicin. It has gained accelerated approval due to its promising clinical results in 2000.

SGN-CD33A (vadastuximab talirine) is an ADC composed of an anti-CD33 monoclonal antibody and a highly potent DNA-binding pyrrolobenzodiazepine dimer. Based on the positive response data, a phase III trial of this ADC in combination with azacitidine or decitabine for older patients with newly diagnosed AML has been initiated.

Structures of SGN-CD33A (vadastuximab talirine) and IMGN779. Fig.2 Structures of SGN-CD33A (vadastuximab talirine) and IMGN779. (Beck, 2017)

IMGN779 is an ADC containing an anti-CD33 monoclonal antibody linked to the novel DNA alkylating molecule DGN462. Preclinical data demonstrated highly specific cytotoxicity against primary AML cells, especially in samples with an FLT-ITD mutation. IMGN779 combined with the PARP inhibitor Olaparib showed enhanced ex vivo activity and a decreased tumor burden in a xenograft mouse model. IMGN779 can enhance bystander killing but without increasing systemic toxicity, and has entered phase I trials.

SGN-CD123A is another ADC with the antibody against CD123. CD123 is overexpressed in AML cells, but restrictively expressed in the healthy hematopoietic compartment, which can decrease off-target toxicities. SGN-CD123A has been tested in phase I trial.

ADCs development services in Creative Biolabs include but not limited to the following targets:

What Can We Do for You?

As the new generation of immunotherapy, ADCs are meticulously constituted bio-macromolecules with high potential in the treatment of cancer such as the leukemia. With novel technology platform and professional scientist team, Creative Biolabs gets ready to provide you the best ADC development services targeting AML treatment. Our featured services also involve design and preparation of customized linker and drug-linker complexes. Please contact us for more information and a detailed quote.

Reference

  1. Beck, A.; et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nature reviews Drug discovery. 2017, 16(5): 315.

Other ADC Development for Leukemia:

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