Construction of Anti-PTK7/MET Bispecific Antibody-Drug Conjugate and Study of Its Antitumor Activity
SHU Ruixue1,2,3, SHANG Chengzhang2, JIN Meiqin1,2,3, SHEN Yuelei2,3*
A BsADC (bispecific antibody-drug conjugate) targeting PTK7 (protein tyrosine kinase 7) and MET (cellular-mesenchymal epithelial transition factor), named P91M32-ADC. P91M32-ADC was constructed by using Biocytogen’s fully human antibody RenLite® mice. Both in vivo and in vitro efficacy were subsequently evaluated. The internalization and anti-tumor efficacy were measured by the FACS (fluorescence activated cell sorting) and Incucyte. This study conjugated the bispecific MET×PTK7 antibody to the monomethyl auristatin E (MMAE payload), by using a Val-Cit (vc) linker, to generate the MET×PTK7 BsADC with an average drug:antibody ratio of approximately 4. Incucyte was used to compare the in vitro anti-tumor ability of P91M32-ADC to ABBV-647 analog-ADC and ABBV-399 analog-ADC. Furthermore, the tumor inhibitory activity of P91M32-ADC in vivo was explored in the tumor-bearing mice model. These results showed that P91M32-ADC has superior internalization and anti-tumor efficacy both in vitro and in vivo compared to ABBV-647 analog-ADC. In this experiment, the ADC drug P91M32-ADC targeting PTK7/MET was successfully constructed and the experimental results showed that P91M32-ADC has the potential to improve the efficacy of PTK7 antibody conjugate.
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