ADC Development Services Targeting CD37

Antibody-drug conjugate (ADC) is an innovative targeted therapeutic agent for cancers. ADCs take advantage of the specificity of the antibody to the antigen on the tumor cells and the potent cytotoxicity of the drug. With years of experience in the field of antibody discovery and organic synthesis, Creative Biolabs provides comprehensive ADCs design and preparation services targeting CD37, and we are capable of providing service from antibody discovery to ADC GMP manufacturing.

Introduction of CD37

As a leukocyte surface antigen, CD37 antigen (TSPAN26) belongs to the tetraspanin superfamily. The antigen is a transmembrane protein encoded by the CD37 gene. CD37 is widely expressed on malignant mature B cells such as the B-cell non-Hodgkin lymphoma (NHL) and B-cell chronic lymphocytic leukemia (B-CLL). Tetraspanins can promote the signaling transduction as a kind of “molecular facilitators”, which also functions in cell growth, survival, adhesion, trafficking, intercellular communication, metastasis, and immune responses. CD37 commonly combines with other tetraspanins and MHC II to forms complexes on B cells and exert its biological functions. Generally, CD37 plays an important role in T-B-cell interaction, IgG/IgA expression, and regulating the immune responses and tolerance.

Fig.1 Schematic representation of the biologic role of CD37 in B cells. (Bertoni, 2016)

Anti-CD37 ADC for NHL

NHL is a cancer of the lymphatic system arising from the lymphocytes. It is more common than Hodgkin’s lymphoma. CD37 is highly expressed on NHL cells, thus, it is considered as a potential therapeutic target in NHL therapy.

AGS67E is one of the ADCs targeting CD37, and it consists of an anti-CD37 human monoclonal IgG2 antibody conjugated to the microtubule-disrupting agent mono-methyl auristatin E (MMAE) via a protease-cleavable linker. This ADC is developed for the treatment of NHL or B/T-cell malignancies. Preclinical trial results showed that AGS67E can induce potent anti-tumor cytotoxicity in various NHL and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples. Importantly, AGS67E demonstrates a favorable extra-medullary safety profile and signs of anti-lymphoma activity in phase I clinical study.

IMGN529 (also known as Naratuximab emtansine) is another ADC development for the treatment of NHL targeting CD37. IMGN529 is composed of the potent antimicrotubule agent maytansinoid (DM1) linked to an anti-CD37 antibody through the thioether linker, N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC). IMGN529 has the specificity of parent antibody and enhanced cytotoxic activity of payload. During the in vitro studies, IMGN529 presented significant G2/M cell cycle arrest after internalization and release of the drug in lysosomal processing. It has highly antitumor activity against subcutaneous B-cell tumor xenografts. Furthermore, in phase II clinical study, IMGN529 also showed effective cytotoxicity to tumor cells in patients with B-cell malignancies including NHL and CLL.

Anti-CD37 ADC for Acute Myeloid Leukemia (AML)

AML is a type of blood cancer starting from the bone marrow. CD37 is well expressed on the AML cells, which is also regarded as a useful marker in the therapy of AML. AGS67E ADC is also investigated in the AML treatment. It is reported that AGS67E can significantly bind to AML cells of the patients and internalize, resulting in cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in AML xenografts. Therefore, AGS67E may serve as a potential therapeutic option for AML.

Fig.2 Structure of AGS67E. (Pereira, 2015)

What Can We Do for You?

ADCs are showing amazing therapeutic promise in cancer treatment. Creative Biolabs is here to help support customers’ ADCs development project. We provide the best ADCs design and construction services against the CD37 with advanced technology platforms, and will apply the first-hand expertise to your distinct project requirements. Our ADCs development services from ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation to ADC in vitro Analysis and ADC in vivo Analysis. If you are interested in our service, please do not hesitate to contact us for more details.

References

1. Bertoni, F.; Stathis, A. Staining the target: CD37 expression in lymphomas. Blood. 2016, 128(26): 3022-3023.
2. Pereira, D. S.; et al. AGS67E, an anti-CD37 monomethyl auristatin E antibody-drug conjugate as a potential therapeutic for B/T-cell malignancies and AML: a new role for CD37 in AML. Molecular cancer therapeutics. 2015, 14(7): 1650-1660.

For Research Use Only. NOT FOR CLINICAL USE.