ADC Development Services Targeting CD74

As a leading service company in the field of antibody-drug conjugates (ADCs) development, Creative Biolabs provides customers ADCs development services and various related products such as the antibody, drug or linker-payload. With over 10 years of experience, Creative Biolabs now provides a fully integrated ADCs design and construction service against the CD74 marker for your cancer research.

Introduction of CD74

CD74, also known as p33, DHLAG or HLADG, is a type II transmembrane glycoprotein. It is encoded by the CD74 gene and is an important chaperone associated with the MHC class II α and β chains to regulate the immune response. CD74 is the cell surface receptor of the cytokine macrophage migration inhibitory factor (MIF) to initiate the survival pathways and cell proliferation. Besides, it also plays a role in the trafficking of MHC class II, which is involved in the B-cell maturation through activation of transcription mediated by the NF-κB p65/RelA homodimer and the coactivator TAFII105. It has been found that CD74 involves in macrophage migration inhibitory factor-induced activation of signaling events, such as phosphorylation of extracellular signal-regulated kinase-1/2 and prostaglandin E2. In addition, CD74 is considered as a potential target in the treatment of a number of cancers due to its overexpression in mutiple cancer cells.

Fig.1 CD74 functions as a receptor for the cytokines macrophage migration inhibitory factor (MIF) and MIF-2. (Schröder, 2016)

Anti-CD74 ADC for Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

IMMU‑110 is an ADC targeting the CD74 antigen which is widely expressed on the NHL and CLL cells. The ADC consists of an anti-CD74 antibody conjugated to the potent toxic drug doxorubicin through a pH‑sensitive linker. Once the ADC combines with CD74 and enters the acidic environment of the tumour cell, it releases a high concentration drug from the mAb to achieve the killing of tumor cells. Clinical studies showed that IMMU-110 can specifically bind to CD74 and present favorable safety and efficacy profile. IMMU-110 is investigated in phase II trials in CLL and NHL currently.

Anti-CD74 ADC for Multiple Myeloma (MM)

CD74 is also well expressed on multiple myeloma cells, thus, ADC for MM has been developed based on the protein. STRO-001 is a novel ADC composed of a fully human aglycosylated anti-CD74 antibody-drug linked to a non-cleavable linker-maytansinoid warhead by a novel cell-free antibody synthesis platform. Preclinical trials demonstrated that the ADC has significant antitumor activity and is a promising therapeutic agent for the treatment of MM. STRO-001 is being clinically investigated in a phase I study of patients with MM and B-cell malignancies currently.

Fig.2 Structures of STRO-001. (Abrahams, 2018)

What Can We Do for You?

As the new generation of immunotherapy, ADCs are considered as one of the most potential therapies in the treatment of cancer and various other diseases. With state of the art development platforms and facilities, Creative Biolabs is capable of providing clients high quality ADCs construction services. Please contact us for more information and a detailed quote.

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. Schröder, B. The multifaceted roles of the invariant chain CD74-More than just a chaperone. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2016, 1863(6): 1269-1281.
2. Abrahams, C. L.; et al. Targeting CD74 in multiple myeloma with the novel, site-specific antibody-drug conjugate STRO-001. Oncotarget. 2018, 9(102): 37700.

For Research Use Only. NOT FOR CLINICAL USE.