Be the most trusted biotech company

Henlius' Innovative Asymmetric Bispecific Antibody CLD Platform Published in Biochemical Engineering Journal


Recently, Henlius has made a breakthrough in asymmetric bispecific antibody cell line development (CLD), and the study results have published in Biochemical Engineering Journal (link). Innovative CLD platform, established by CLD/PEX Director Yanling Wang, and the team from Henlus’ US Innovation Center, demonstrated a simple and effective way to obtain high-yield and high-quality cell lines for asymmetric antibody production. In this platform, over 90% of clones expressed the desired products, and stable monoclonal cell line increased the titer to 6g/L, such results have exceeded the industry's average level.

Research and development of bispecific antibodies are gaining momentum in the pharmaceutical industry in recent decades, and the asymmetric format is one of its subcategories showing great potential. However, for traditional random integration (RI) -based CLD platforms, expression of correctly assembled asymmetric antibodies remains challenging. Therefore, to design and express HLX101, the company combined Leap-In Transposase® technology, a novel transposon-based integration strategy with “dual” and “quad” expression vector designs, and a microcapillary electrophoresis (µM) based high-throughput screening method, which efficiently identified clones expressing heterodimers at early stages of CLD. HLX101 is an asymmetric fusion antibody, developed by Henlius independently, composed of two different heavy chains and two common light chains. Knobs-into-holes (KiH) mutations were designed in the CH3 region, and the C-terminal of heavy chain-knob has a cytokine attached and the heavy chain-hole does not.


The stable cell line platform established by Henlius was significantly improved in purity, titer, and the percentage of single clones expressing desired products. The percentage of single clones expressing desired heterodimer was increased from 6% to 90%. The final titer of a single clone fed-batch production reached 6g/L with fewer product related impurities. Herein, an inspired CLD strategy was developed for asymmetric multichain bispecific antibodies, improving the overall screening efficiency and candidate clone quality and laying a firm foundation for innovative product development.


Henlius continues enhancing internal innovation capacities and external collaboration with more strategic partners. The two innovation centres of Henlius, located in China and the US work closely and support each other to enhance R&D efficiency. With antibody technology as the core, Henlius proactively explores immuno-oncology combination therapy, bispecific antibodies, and antibody-drug conjugates (ADC) to enrich diversified product pipeline, providing innovative and affordable medicines to meet global medical needs.


About Biochemical Engineering Journal

The Biochemical Engineering Journal (IF 4.446)aims to promote progress in the crucial chemical engineering aspects of the development of biological processes associated with everything from raw materials preparation to product recovery relevant to industries as diverse as medical/healthcare, industrial biotechnology, and environmental biotechnology.