ADC Development Services Targeting ENPP3

Antibody-drug conjugates (ADCs) represent a novel and promising class of biotherapeutics for the treatment of cancer. Potent drugs combine with antibodies through suitable linkers to generate specific therapeutic molecules-ADC, in which the antibody confers cell specificity and extended serum half-life while the payload displays a potent antitumor activity. Creative Biolabs is committed to developing high-quality ADC based on our advanced technology platforms. Our ADCs development services include the production of specific antibody, the synthesis of quality-guaranteed linker-payload and effective conjugation. We believe our services will promote your innovative cancer treatment.

Introduction of ENPP3

ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3), also known as CD203c, is a type II transmembrane protein as an enzyme in human. It is encoded by the ENPP3 gene and belongs to the ectonucleotide pyrophosphatases/phosphodiesterases family serving as a basophil activation marker. ENPP3 protein is composed of an extracellular domain, a nuclease-like domain, a catalytic domain and a somatomedin B-like domain. ENPP3 plays a role in glycosyltransferase activity through hydrolyzing extracellular pyrophosphate, phosphodiester bonds and intracellular nucleotides. It is expressed by neoplastic mast cells during mastocytosis, acute basophilic leukemia, colon cancer, and bile duct, and it has been found highly expressed in renal cell carcinoma (RCC) while low or absent in normal tissues. Thus, ENPP3 is considered as a potential target for the treatment of RCC.

Fig.1 Crystal structure and substrate binding mode of ENPP3. (Döhler, 2018)

Anti-ENPP3 ADC in RCC

ENPP3 has been used in several ADCs development as a target for the RCC therapy, which is expressed by most RCCs of clear cell histology and papillary histology. AGS-16M8F and AGS-16C3F represent novel ADCs targeting this protein, consisting of fully human anti-ENPP3 IgG2a antibodies linked to maleimidocaproyl monomethyl auristatin F (MMAF) through a noncleavable linker. Preclinical trials demonstrated that both ADCs can be internalized significantly to induce cytotoxicity in both in vitro and in vivo models of RCC. Besides, in the phase I study of the AGS-16CF, results showed that the ADC has potent antitumor activity in a heavily pretreated, refractory RCC population. Thus, AGS-16C3F could be a potential new treatment for the RCC.

Fig.2 Internalization of AGS16F by KU812 cells. AGS16F was incubated with KU812 cells, then fixed and stained as indicated. (Doñate, 2016)

Anti-ENPP3 ADC in Liver Carcinoma

AGS16F is a novel antibody-drug conjugate directed against ENPP3, which is comprised of anti-ENPP3 IgG2 antibody (AGS16-7.8) conjugated with MMAF via a noncleavable linker (mcMMAF). Preclinical trials were performed including the binding and internalization assays, cytotoxicity assays, and tumor growth inhibition in mouse xenograft models to assess the therapeutic potential for liver carcinoma and RCC. Results demonstrated that AGS16F significantly inhibited tumor growth, which can specifically localize to tumors and induce cell cycle arrest and apoptosis.

What Can We Do for You?

Creative Biolabs offers ADCs development services against the ENPP3 biomarker to accelerate your drug discovery program. It is our commitment to give you high-quality products with fast turnaround time. Our experienced scientist team along with our broad services portfolio makes it easier to meet your specific requirements. Dedicated ADC experts in Creative Biolabs will provide you reliable services and strict quality controls under the most competitive price. Our ADCs services include ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation, ADC in vitro Analysis and ADC in vivo Analysis.

If you have any special requirements related to ADCs, please feel free to contact us. We are looking forward to working together with your attractive projects.

References

1. Döhler, C.; et al. Crystal structure and substrate binding mode of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3). Scientific reports. 2018, 8(1): 10874.
2. Doñate, F.; et al. AGS16F is a novel antibody drug conjugate directed against ENPP3 for the treatment of renal cell carcinoma. Clinical Cancer Research. 2016, 22(8): 1989-1999.

For Research Use Only. NOT FOR CLINICAL USE.