top of page
Speakers
Click on individual speaker to view abstract.
Professor Dr. Musheng Zeng
Development of neutralizing antibodies and novel vaccines targeting EBV and its associated diseases
Abstract: Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.
Abstract: Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.
Associate Professor Dr. Jeannie Wong
Prediction of “Trigger Point” for Adaptive Radiotherapy (ART) of Nasopharyngeal Carcinoma (NPC) - a radiomics approach
Abstract: Radical radiotherapy stands as the primary approach in managing nasopharyngeal carcinoma (NPC), involving a standard regimen of seven weeks of fractionated radiation treatment. However, significant anatomical changes in the tumour and surrounding tissues can occur throughout treatment, rendering the originally planned dose delivery ineffective. Adaptive radiotherapy (ART) has emerged to address this challenge, involving rescanning and replanning treatments to accommodate these structural changes. At its core, ART allows for treatment adjustments in response to a change in the patient, which can be considered a “signal”, indicating that certain features of the patient's anatomy had changed from the original state at the time of planning. However, a key issue in ART for NPC lies in determining the appropriate trigger point for action. Currently, the clinical staff often rely on subjective visual observations. Thus, there is a need to evaluate the impact of anatomical changes in NPC patients undergoing radiotherapy to emphasise the necessity of an objective trigger point for corrective actions during treatment. Using radiomics and machine learning-based predictions may provide new insights into identifying useful “trigger points” for ART, thereby enhancing precision in radiotherapy delivery and improving treatment efficacy and the quality of life for NPC patients
Abstract: Radical radiotherapy stands as the primary approach in managing nasopharyngeal carcinoma (NPC), involving a standard regimen of seven weeks of fractionated radiation treatment. However, significant anatomical changes in the tumour and surrounding tissues can occur throughout treatment, rendering the originally planned dose delivery ineffective. Adaptive radiotherapy (ART) has emerged to address this challenge, involving rescanning and replanning treatments to accommodate these structural changes. At its core, ART allows for treatment adjustments in response to a change in the patient, which can be considered a “signal”, indicating that certain features of the patient's anatomy had changed from the original state at the time of planning. However, a key issue in ART for NPC lies in determining the appropriate trigger point for action. Currently, the clinical staff often rely on subjective visual observations. Thus, there is a need to evaluate the impact of anatomical changes in NPC patients undergoing radiotherapy to emphasise the necessity of an objective trigger point for corrective actions during treatment. Using radiomics and machine learning-based predictions may provide new insights into identifying useful “trigger points” for ART, thereby enhancing precision in radiotherapy delivery and improving treatment efficacy and the quality of life for NPC patients
Dr. Susan Hoe Ling Ling
Cancer’s complexity: The role of mouse models in unveiling it
Abstract: Cancer research relies heavily on animal models to understand disease mechanisms, test potential therapies, and explore new treatment modalities. By examining the details of mouse models, this presentation aims to shed light on their applications in cancer research, focusing on patient-derived xenografts (PDXs) in particular. Beginning with an overview of available animal models for cancer research, it will progress to discuss the fundamentals of PDX models in mice, their general methodology, advantages and limitations. IMR’s experience in establishing several PDX models for nasopharyngeal carcinoma (NPC), their characterisation, and usage will be also highlighted. Beyond PDXs, relevant topics such as patient-derived organoids, and the ethical considerations surrounding animal research will be discussed. It is hoped that increased understanding of the indispensable role of mouse and other animal models, balanced with their proper and ethical use in cancer research, will ultimately pave the way for developing more targeted and effective therapies for patients.
Abstract: Cancer research relies heavily on animal models to understand disease mechanisms, test potential therapies, and explore new treatment modalities. By examining the details of mouse models, this presentation aims to shed light on their applications in cancer research, focusing on patient-derived xenografts (PDXs) in particular. Beginning with an overview of available animal models for cancer research, it will progress to discuss the fundamentals of PDX models in mice, their general methodology, advantages and limitations. IMR’s experience in establishing several PDX models for nasopharyngeal carcinoma (NPC), their characterisation, and usage will be also highlighted. Beyond PDXs, relevant topics such as patient-derived organoids, and the ethical considerations surrounding animal research will be discussed. It is hoped that increased understanding of the indispensable role of mouse and other animal models, balanced with their proper and ethical use in cancer research, will ultimately pave the way for developing more targeted and effective therapies for patients.
Professor Dr. Ian Paterson
Function and mechanisms of activation of cancer-associated fibroblasts from NPC
Abstract: It is now recognised that non-malignant components within the tumour microenvironment (TME) also influence tumour development and progression. In some epithelial tumours, cancer-associated fibroblasts (CAFs) can be the most abundant cell type within the tumour stroma. Here, they actively participate in the reciprocal communication between tumour cells and other host cells in the TME to create a tumour-permissive microenvironment. CAFs share many characteristics with fibroblasts found within healing wounds and demonstrate a perpetually “active,” alpha-smooth muscle actin positive phenotype. In this talk, I will describe some of the functions of NPC-derived CAFs and how tumour-derived factors activate normal fibroblasts via the sphingosine 1-phosphate signalling pathway. Finally, the possibility of targeting CAFs therapeutically will be discussed.
Abstract: It is now recognised that non-malignant components within the tumour microenvironment (TME) also influence tumour development and progression. In some epithelial tumours, cancer-associated fibroblasts (CAFs) can be the most abundant cell type within the tumour stroma. Here, they actively participate in the reciprocal communication between tumour cells and other host cells in the TME to create a tumour-permissive microenvironment. CAFs share many characteristics with fibroblasts found within healing wounds and demonstrate a perpetually “active,” alpha-smooth muscle actin positive phenotype. In this talk, I will describe some of the functions of NPC-derived CAFs and how tumour-derived factors activate normal fibroblasts via the sphingosine 1-phosphate signalling pathway. Finally, the possibility of targeting CAFs therapeutically will be discussed.
Associate Professor Dr. Melvin Lee Kiang Chua
Future of Personalised therapies in NPC
Abstract: In the past decade, large-scale genomics studies have revealed the mutational landscape of NPC tumours that is largely shaped by prior infection of Epstein-Barr virus (EBV) in the tumour and immune cells. Consequently, the mutational profile of NPC bears certain hallmarks like genomic instability, epigenetic hypermethylation, and structural rearrangements. Despite these advances in knowledge, there remains very few targeted therapeutics that are efficacious in NPC.
In my talk, I will discuss some of the novel strategies that were uncovered through molecular profiling studies, and are currently under investigation. They include targeting the aberrant pathways that are linked to EBV co-infection, as well as modulating the immune environment that are host-agonist.
Abstract: In the past decade, large-scale genomics studies have revealed the mutational landscape of NPC tumours that is largely shaped by prior infection of Epstein-Barr virus (EBV) in the tumour and immune cells. Consequently, the mutational profile of NPC bears certain hallmarks like genomic instability, epigenetic hypermethylation, and structural rearrangements. Despite these advances in knowledge, there remains very few targeted therapeutics that are efficacious in NPC.
In my talk, I will discuss some of the novel strategies that were uncovered through molecular profiling studies, and are currently under investigation. They include targeting the aberrant pathways that are linked to EBV co-infection, as well as modulating the immune environment that are host-agonist.
Dr. David Lee Dai Wee
Challenges in the management of nasopharyngeal cancer – Malaysian perspective
Abstract: Nasopharyngeal cancer (NPC) poses significant challenges in management in Malaysia. This lecture explores the unique aspects of NPC management from a Malaysian perspective. Factors such as epidemiology, cultural influences, socioeconomic disparities, and healthcare infrastructure significantly impact diagnosis, treatment, and outcomes. Challenges in early detection due to non-specific symptoms, limited access to healthcare in rural areas, and cultural beliefs affecting healthcare-seeking behaviors. The treatment modalities including radiotherapy, chemotherapy, and surgery, are complex, considering their effectiveness, side effects, and accessibility within the Malaysian healthcare system. Moreover, the role of multidisciplinary teams, patient education, and support networks in overcoming these challenges is emphasized. We aim to foster a better understanding and improve outcomes for patients with NPC.
Abstract: Nasopharyngeal cancer (NPC) poses significant challenges in management in Malaysia. This lecture explores the unique aspects of NPC management from a Malaysian perspective. Factors such as epidemiology, cultural influences, socioeconomic disparities, and healthcare infrastructure significantly impact diagnosis, treatment, and outcomes. Challenges in early detection due to non-specific symptoms, limited access to healthcare in rural areas, and cultural beliefs affecting healthcare-seeking behaviors. The treatment modalities including radiotherapy, chemotherapy, and surgery, are complex, considering their effectiveness, side effects, and accessibility within the Malaysian healthcare system. Moreover, the role of multidisciplinary teams, patient education, and support networks in overcoming these challenges is emphasized. We aim to foster a better understanding and improve outcomes for patients with NPC.
Ms Looi Chin King
Inflammasomes as epigenetically-regulated mediators of tumour cell-intrinsic immune evasion in nasopharyngeal carcinoma
Abstract: Nasopharyngeal carcinoma (NPC) is predominantly diagnosed in South China and South Asia. Recent studies have revealed that epigenetic modifications play critical roles in regulating anticancer immune response as well as immune evasion, suggesting that targeting epigenetic regulators might be promising strategy to repair T-cell dysfunction. In this study, we evaluated the epigenetic changes in the EBV-positive NPC cells with acquired resistance against cytotoxic T lymphocytes (CTL), and identified tumour cell-intrinsic immune evasion pathways that were regulated by epigenetic alterations.
Using an antigen-independent CTL assay, our team recently generated and validated two EBV-positive NPC cell lines (C666-1 and NPC43) with acquired resistance against T-cell mediated tumour lysis. DNA methylation analyses were conducted to investigate the epigenetic events that could drive the NPC cell resistance to CTL-mediated cytotoxicity. The identified candidate genes that exhibiting epigenetic alterations were further investigated via RT-PCR, immunoblotting and RNAi-based functional studies.
We identified NLRP1 and NLRP3 inflammasomes as potential key targets of epigenetically regulated tumour cell-intrinsic immune evasion in EBV-positive NPC cells. These epigenetic-regulated proteins could serve as promising therapeutic target for NPC treatment, which warrants further investigations.
Abstract: Nasopharyngeal carcinoma (NPC) is predominantly diagnosed in South China and South Asia. Recent studies have revealed that epigenetic modifications play critical roles in regulating anticancer immune response as well as immune evasion, suggesting that targeting epigenetic regulators might be promising strategy to repair T-cell dysfunction. In this study, we evaluated the epigenetic changes in the EBV-positive NPC cells with acquired resistance against cytotoxic T lymphocytes (CTL), and identified tumour cell-intrinsic immune evasion pathways that were regulated by epigenetic alterations.
Using an antigen-independent CTL assay, our team recently generated and validated two EBV-positive NPC cell lines (C666-1 and NPC43) with acquired resistance against T-cell mediated tumour lysis. DNA methylation analyses were conducted to investigate the epigenetic events that could drive the NPC cell resistance to CTL-mediated cytotoxicity. The identified candidate genes that exhibiting epigenetic alterations were further investigated via RT-PCR, immunoblotting and RNAi-based functional studies.
We identified NLRP1 and NLRP3 inflammasomes as potential key targets of epigenetically regulated tumour cell-intrinsic immune evasion in EBV-positive NPC cells. These epigenetic-regulated proteins could serve as promising therapeutic target for NPC treatment, which warrants further investigations.
Professor Dr. Sumei Cao
A novel EBV Cp methylation test for early detection and
triaging high-risk populations in screening for NPC
Abstract: Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is
prevalent in Southern China. The NPC screening strategy based on
immunoglobulin A (IgA) antibodies of Epstein-Barr nuclear antigen 1
(EBNA1) and viral capsid antigen (VCA) has been officially endorsed for
NPC screening in the Chinese mainland. However, EBV serology screening
strategy is hindered by a low positive predictive value (PPV) of less than
5%. To address this, professor Sumei Cao and her colleagues developed a
novel swab-based EBV Cp methylation quantification (E-CpMQ) assay for
triaging the EBV seropositive individuals and NPC early detection. In a
case-control study, E-CpMQ demonstrated impressive sensitivity and
specificity rates of 96.4% and 89.8%, respectively. Crucially, it effectively
discerned between benign and malignant lesions in the nasopharynx,
boasting over 93% sensitivity in both early- and late-stage NPC. In a
prospective cohort study, the sensitivity and specificity of E-CpMQ in
seropositive individuals are both over 90%, with a remarkable positive
predictive value (PPV) reaching 50%. Moreover, individuals with positive for
EBV Cp methylation have a five-year risk of developing NPC close to 100
times than that of individuals who are negative. Notably, its performance
significantly surpassed that of the existing triage indicators of EBV-DNA
load test based on nasopharyngeal swabs. In summation, the E-CpMQ
assay enables accurate and reproducible EBV Cp methylation ratio
quantification and offers a sensitive, specific, cost-effective method for
NPC early detection and triaging seropositive individuals.
triaging high-risk populations in screening for NPC
Abstract: Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is
prevalent in Southern China. The NPC screening strategy based on
immunoglobulin A (IgA) antibodies of Epstein-Barr nuclear antigen 1
(EBNA1) and viral capsid antigen (VCA) has been officially endorsed for
NPC screening in the Chinese mainland. However, EBV serology screening
strategy is hindered by a low positive predictive value (PPV) of less than
5%. To address this, professor Sumei Cao and her colleagues developed a
novel swab-based EBV Cp methylation quantification (E-CpMQ) assay for
triaging the EBV seropositive individuals and NPC early detection. In a
case-control study, E-CpMQ demonstrated impressive sensitivity and
specificity rates of 96.4% and 89.8%, respectively. Crucially, it effectively
discerned between benign and malignant lesions in the nasopharynx,
boasting over 93% sensitivity in both early- and late-stage NPC. In a
prospective cohort study, the sensitivity and specificity of E-CpMQ in
seropositive individuals are both over 90%, with a remarkable positive
predictive value (PPV) reaching 50%. Moreover, individuals with positive for
EBV Cp methylation have a five-year risk of developing NPC close to 100
times than that of individuals who are negative. Notably, its performance
significantly surpassed that of the existing triage indicators of EBV-DNA
load test based on nasopharyngeal swabs. In summation, the E-CpMQ
assay enables accurate and reproducible EBV Cp methylation ratio
quantification and offers a sensitive, specific, cost-effective method for
NPC early detection and triaging seropositive individuals.
Ms Tianbi Duan
Achieving true single-cell spatial whole transcriptome profiling for diverse biological applications using Stereo-seq
Abstract: Developed by STOmics, Stereo-seq is a world-leading spatial biology technology. By achieving multi-centimeter field of view combined with nanoscale resolution for unbiased in situ whole transcriptome studies of organisms and tissues, Stereo-seq offers diverse application solutions to revolutionize life sciences research and clinical applications. In this talk, we'll introduce Stereo-seq as an innovative spatial technology, present various product solutions that are currently being offered by STOmics around the globe, and discuss recent publications and user cases using Stereo-seq.
Abstract: Developed by STOmics, Stereo-seq is a world-leading spatial biology technology. By achieving multi-centimeter field of view combined with nanoscale resolution for unbiased in situ whole transcriptome studies of organisms and tissues, Stereo-seq offers diverse application solutions to revolutionize life sciences research and clinical applications. In this talk, we'll introduce Stereo-seq as an innovative spatial technology, present various product solutions that are currently being offered by STOmics around the globe, and discuss recent publications and user cases using Stereo-seq.
bottom of page