Victoria Cheung
PIPS Host Organisation: CEAR (Centre of Excellence for Antibody Research), Faculty of Tropical Medicine, Mahidol University, Bangkok
Project Title: Development of mAb Therapeutics to Combat Dengue Virus and SARS-CoV-2

This placement focused on human monoclonal antibody (HuMab) therapy to fight against Dengue Virus (DENV), where approximately 3.9 billion people currently live in dengue-endemic countries. Severe dengue can manifest in victims and cause plasma leakage, respiratory distress, and organ impairment, and is a leading cause of death in some Asian and Latin American countries. No specific treatment for all four serotypes of DENV is available. In terms of virion structure, two proteins play a distinctive role in DENV disease progression: Envelope (E) glycoprotein, which serves as a major surface binding area for neutralising antibodies, and Non-structural protein 1 (NS1), which exacerbates immune evasion, pathogenesis, and viral replication.

The three-month iPIPS project targeted the production of a recombinant IgG of a candidate HuMab clone exhibiting both anti-NS1 properties and cross-reaction with E protein for the development of second-generation monoclonal antibody therapeutics to combat severe dengue. Specifically, this project aimed to aid HuMAb and recombinant IgG characterization in vitro using neutralization, ELISA, ADE assays, and epitope mapping techniques by inserting candidate MAb genes into vectors to express in CHO cells. This approach would fast-track conventional methods using PBMC from patients for therapeutic monoclonal antibody preparation using hybridoma technology.

Other ongoing projects Victoria was simultaneously exposed to include the development of a dengue mouse model to engineer mice susceptible to viral infection/ADE effect to test the effectiveness of the therapeutic mAb and phage display techniques (biopanning) during ongoing research with WT Covid-19 and Omicron.

The research at CEAR fits into a wider societal context by broadening Victoria’s understanding of the global impact of tropical diseases in tropical and subtropical climates. She gained an understanding of the challenges in tackling epidemic-scale problems in developing countries with limited resources. Notably, the fatality rate of severe dengue can be reduced to under 1% with accessible medical care and early detection of disease progression.

Techniques Victoria was exposed to, such as phage display, mouse handling, and hybridoma technology in SPYMEG fusion cells and PBMC isolation, introduced her to a different world of techniques and the skills required to produce a therapeutic monoclonal antibody. Helping develop their second-generation mAb using molecular cloning techniques facilitated building her professional networks internationally. She also gained unique insights into the role of a director at a top university research centre and learned the direction taken to translate their therapeutic research into commercialization.

Victoria’s experience at BIOTEC provided first-hand insight into the therapeutic drug launch timeline and the tenacity required from novel findings and characterization in a research lab, acquiring patents and proof of concept (2008-2019) to GMP production, clinical trials, FDA approval, and commercialization of therapeutics for clinical use (2019-2028), with a market release expected by 2028. She learned the importance of collaborating with a licensing company to help with the latter stages of drug development, from proof of concept, safety and toxicity dose finding, clinical trials, and FDA approval.

Victoria also learned about the Thai market landscape, its growth, and its dependency on foreign expertise, and how it aims to transition creating more research-driven products. She realised that having more company investment instead of government funding would accelerate market translation, as companies are results-driven. Government subsidies, while beneficial, can slow progress due to procedural delays.

In terms of broader commercial awareness, the transparency in costs demonstrated by Professor Pongrama in achieving key milestones to commercialisation highlighted the financial impacts on the pipeline of events and the necessity of international collaboration and cooperation for successful outcomes.

During her three months in Bangkok, Victoria established invaluable international professional networks, experienced and understood Thai culture, appreciated cultural differences, and overcame language barriers. She was warmly welcomed by the team, who shared their rich culture with her. Reciprocating by answering their questions about the UK and sharing English culture was rewarding. Victoria also gained awareness of the developed areas in Bangkok, which contrasted with media portrayals of poverty, showcasing the city’s metropolitan nature and wealth.

This experience provided Victoria with invaluable perspective for her future career, reinforcing and developing her adaptability to significant changes in working and living environments.