Development and Efficacy Evaluation of Therapeutic Monoclonal Antibodies Targeting Autotaxin

Professor Xu, Aimin   (Principal Investigator (PI))

24

2024-02-01

1800706

Development and Efficacy Evaluation of Therapeutic Monoclonal Antibodies Targeting Autotaxin

Efficacy, Therapeutic, Monoclonal, Antibodies, Autotaxin

Biology and Medicine

MHP/117/22

Mainland-Hong Kong Joint Funding Scheme (MHKJFS)

2023

On-going

Monoclonal antibody (mAb)-based drugs are the mainstay of modern biopharmaceuticalindustry. However, only a handful of molecular targets have been validated for mAbdevelopment. Our group has obtained solid preclinical evidence that antibodyneutralization of autotaxin, a secreted enzyme hydrolyzes lysophosphatidylcholine toproduce lysophosphatidic acid (LPA), is effective for treatment of several hardly-curablediseases including obesity-related liver fibrosis and ischemic stroke. Furthermore, wehave generated two mAb candidates with neutralizing activity against autotaxin. Thisproject aims to (1) develop and characterize humanized anti-autotaxin mAbs with highaffinity and potent pharmacological activity using genetic engineering, phage display andthe immunoglobulin gene humanized mice, and (2) to conduct preclinical evaluation forthe pharmacodynamics and pharmacologic effects of these mAbs in treating liver fibrosisand stroke. This study will be the first to develop mAb-based pharmacotherapy targetingautotaxin, thus avoiding the strong toxicity and low specificity of small-molecule autotaxininhibitors. As the prevalence of obesity-related liver fibrosis and stroke is rapidlyincreasing globally, development of these mAb drugs is expected to hold huge marketpotential and contribute to the biopharmaceutical development of our country.