PEGylated Bispecific ADC Technology

Over the past decade, ADC therapies have demonstrated much improved target selectivity and efficacy. The goal of ADC technology is solving the toxicity issue inherent in small molecule drug. Many factors contribute to the ADC’s toxicity such as random conjugation, premature release of payload, Fc related toxicity, on-target/off-tumor toxicity etc. Because of systemic toxicity, poor selectivity of biomarkers for patients, and acquired drug resistance, there is urgent need for next generation ADC technology.
Shenzhen Enduring LTD has developed several novel PEGylated BsADCs (P-BsADC), prepared by conjugating a fusion protein of two-scFvs, which target at two different epitopes of receptors or two different receptors, with a pegylated cytotoxic payload. As expected, P-BsADCs are homogeneous without any Fc related toxicity encountered by traditional ADCs and demonstrate excellent in-vitro cytotoxicity and in-vivo inhibition of xenograft tumor. P-BsADCs are stable, showing no detectable release of the payload when incubating with human PBMC for a week at 37 oC. P-BsADCs also demonstrate efficient tumor penetration, accelerated internalization without detectable efflux, suggesting improved endosome and lysosome trafficking. In addition, P-BsADCs do not generate cytotoxicity to megakaryocyte Dam cell line as traditional ADCs do and are less toxic to the non-cancerous HaCaT cells than T-DM1 or DS-8201.