Discovering and optimizing antibody therapeutics against cancers with synthetic antibody libraries
Hong-Sen Chen, Shin-Chen Hou, Hung-Pin Peng, and An-Suei Yang*
Genomics Research Center, Academia Sinica, Taipei, Taiwan
Antibody-based therapeutics are rapidly becoming the major class of biopharmaceuticals treating diverse diseases in humans; there are critical needs of an effective antibody discovery platform for developing novel antibody therapeutics/diagnostics. We have developed antibody discovery platform with the core technology based on the phage-displayed synthetic antibody libraries1,2, which are designed with bioinformatics extracting knowledge from natural antibody repertoires1~3. The effectiveness of the technological platform has been demonstrated in developing tumor cell-specific antibody therapeutics: synthetic antibody repertoires can be advantageous over natural antibody repertoires in generating antibodies suitable for target-specific cancer cell-killing, for which the efficacy is determined with the adaptor systems specifically coupled with the synthetic antibody repertoires in high throughput cell-based assays4. These results show that the synthetic antibody libraries, coupled with the adaptor systems, constitute an effective technological platform capable of engineering novel and optimal antibodies as therapeutics against cancers in humans.
1Hong-Sen Chen, et al (2015), “Predominant structural configuration in natural antibody repertoires enables potent antibody responses against protein antigens”, Scientific Reports5: 12411.
2Chao-Ping Tung, et al (2015), ‘Discovering neutralizing antibodies targeting at the stem epitope of influenza hemagglutinin with synthetic phage-displayed antibody libraries’ Scientific Reports5: 15053.
3Hung-Pin Peng, Kuo Hao Lee, Jhih-Wei Jian, An-Suei Yang*. (2014) “Origins of specificity and affinity in antibody-protein interactions”, PNAS111: E2656-E2665
4Shin-Chen Hou, et al (2016) ‘High throughput cytotoxicity screening of anti-HER2 immunotoxins conjugated with antibody fragments from phage-displayed synthetic antibody libraries’, Scientific Reports6: 31878.