Abstract
Antibody-Drug Conjugation (ADC) is a rapidly growing area and has been widely explored for cancer therapy. In the past decade, numerous progresses have been reported on the identification of proper antibodies, targets validation, discovery of novel payloads, improvement of linkers, as well as the development of new coupling techniques.
We have developed novel conjugation methods, C-lock, K-lock and the combination of the two. C-LockTM conjugation method utilizes a novel linker chemistry to re-connect the reduced disulfide bonds between antibody heavy and light chains, and in the meantime, to introduce a drug to each disulfide bond. While K-LockTM conjugation method is a linker-controlled conjugation technology highly selective on 1 or 2 particular sites among 80-90 Lys side chains of an antibody. The generated ADCs have fewer regioisomers and lower DAR (Drug-Antibody Ratio) while maintaining comparable potency to ADCs from regular conjugation methods. Further purification will give rise to site-specific homogeneous products without needs for cell engineering or enzymatic modification steps. The lead ADCs generated by these technologies showed improved activity both in vitro and in vivo in relevant tumor models, and also exhibited less toxicity compared to commercial standard.
To pursue to the next level, we are currently developing dual drug ADCs which have two different payloads conjugated to single antibody; as well as bi-specific ADCs with either single or dual drug conjugations (2nd generation or ADC-2X). Initial results indicated that these ADCs showed improved activity and specificity in relevant tumor cell lines compared to 1st generation ADCs. Detailed results will be reported. All these data proved that our ADC technologies are unique and superior in antibody drug conjugation and are promising for anti-cancer drug development.
Citation Format: Gang Chen, Tong Zhu, Dylan Deng, Hong Zhang, David Miao. Development of anti-cancer ADCs with Concortis’ C-and K-lock technology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 635. doi:10.1158/1538-7445.AM2015-635
