Guests

For this new edition, we are very pleased to welcome :

"I have been working in the field of tumor immunology since the beginning of my PhD training at Toulouse III – Paul Sabatier University. I focused particularly on tumor antigen (Ag)-specific T cells starting from my postdoctoral training at the Ludwig Institute for Cancer Research in Switzerland. At the time, the Ludwig Institute and the Cancer Research Institute partnered to create the Cancer Vaccine Collaborative (CVC) consortium aimed at developing cancer vaccines. I joined Columbia University as a tenure track assistant professor to initiate a research group and a CVC site. In 2007 I came back to France on an academic Inserm/INCa chair “Chercheurs de haut niveau" and pursued my activity in France, first as Inserm Research Director (DR) in Nantes and Paris and, since 2017, as University Professor – Hospital Practitioner (PU-PH) in Toulouse. I have been leading a research group since 2003. I currently head the “Tumor Immunity and Immunotherapy” team at The Cancer Research Center of Toulouse (CRCT) and the “Immune monitoring core facility” at the Institut Universitaire du Cancer de Toulouse – Oncopole (IUCT-O). I teach immunology at the department of pharmaceutical sciences in the Faculty of health.

My group contributed to the appraisal of the role of spontaneous T-cell responses to tumor Ags in cancer. Within international consortia, we implemented and monitored vaccine trials. Our basic studies led to the identification of human naïve Treg and contributed to our understanding of the ties between Treg and Th17 and their role in cancer. Currently, we focus on deciphering the mechanisms limiting the efficacy of tumor Ag-specific T cells, on understanding their contribution to immune checkpoint blockade clinical efficacy and on translating our findings into clinical trials."

Maha AYYOUB

Therapeutic cancer vaccines : the road to clinical success

In the 1980s, it became clear that cytotoxic T lymphocytes (CTL) play a central role in tumor control. The identification of their targets, i.e., tumor antigens, in the 1990s, set the grounds for the development of therapeutic cancer vaccines aiming at eliciting or boosting tumor-specific CTL in cancer patients. Two decades of research in the cancer vaccine field led to several immunogenic formulations, including recombinant proteins administered with strong adjuvants as well as recombinant viruses and mRNA vaccines encoding tumor antigens. While these immunogenic formulations represented a major milestone, clinical trials failed to demonstrate their clinical efficacy in cancer control. It is noteworthy, however, that these formulations turned out instrumental for the rapid development of SARS-CoV-2 vaccines and for the control of the COVID-19 pandemic.

In parallel, the identification of inhibitory receptors expressed by CTL and other immune cell populations, termed immune checkpoints, and the elucidation of their role in tumor escape, led to the development of immunotherapy by immune checkpoint blockade (ICB) based on monoclonal antibodies which inhibit the interaction between immune checkpoints and their ligands, such as those inhibiting the PD-1/PD-L1 axis. In less than a decade, ICB was introduced for the management of nearly 20 cancer types and became the standard frontline treatment for, up till then, uncurable cancers such as metastatic melanoma and non-small cell lung cancer. Importantly, ICB demonstrated that immunotherapy-mediated tumor rejection is attainable through mobilization of anti-tumor CTL. Nonetheless, clinical benefit from ICB is observed in only a fraction of patients. Chiefly those with preexisting tumor-specific CTL. This undeniable turning point in cancer therapy has restimulated the clinical development of anti-cancer vaccines. In addition, the search for biomarkers of response to ICB, together with major recent advances in next generation DNA/RNA sequencing technologies (NGS), brought to center stage one category of tumor antigens, namely neoantigens encoded by tumoral somatic mutations. NGS, together with high throughput vaccine production processes, concurred to the rapid implementation of neoantigen-based personalized vaccines, some of which are currently in advanced stages of clinical development. Another important lesson learned from ICB is their greater efficacy when administered early in disease management, inferring that early introduction of therapeutic cancer vaccines could also enhance their clinical efficacy. Finally, the advent of ICB creates a momentum for combing them with cancer vaccines, with high potential for increased clinical benefit ensuing from synergy, whereby ICB will increase vaccine immunogenicity and, in turn, immunogenic vaccines will increase the number of patients with CTL responses to tumor antigens who will hence become responsive to ICB.

In my talk, I will trace the major milestones of cancer vaccine formulations development and I will present recent advances in their clinical development which hold high promise for their foreseeable introduction into the anticancer therapeutic armamentarium.

Olivier DUTOUR

Biological anthropology of human infections

Biological anthropology of human infections is a field of study that investigates the interactions between humans and infectious diseases from an anthropological perspective. It combines biological, cultural, and social factors to understand the impact of infections on human populations throughout history and across different societies.

Researchers in this field examine various aspects related to human infections, including the epidemiology and transmission of diseases, host-pathogen interactions, immunological responses, evolutionary perspectives, and the cultural and social dimensions of disease. They explore how infections shape human biology, behavior, and society, as well as how cultural practices and social factors influence disease spread and management.

Biological anthropologists studying human infections often employ multidisciplinary approaches, drawing on methods and theories from genetics, microbiology, archaeology, anthropology, epidemiology, and other related disciplines. They may analyze ancient DNA from archaeological remains to identify pathogens and study disease patterns in past populations. They also investigate contemporary infectious diseases to understand their impact on communities and identify strategies for prevention and control.

The research conducted in the biological anthropology of human infections contributes to our understanding of the complex relationship between humans and pathogens. It provides insights into the evolutionary history of diseases, the adaptation of humans to infectious agents, the cultural and social factors influencing disease dynamics, and the development of strategies for disease prevention and management.

Olivier Dutour is a French archaeologist specializing in prehistory and biological anthropology. His career has been dedicated to studying ancient hominids, funerary practices, human evolution, and the interactions between populations and their environments.

Throughout his work, Dutour has conducted extensive research on human skeletal remains, analyzing their morphology, pathology, and paleodietary patterns to gain insights into the lives and behaviors of past populations. He has made significant contributions to the understanding of Neanderthal anatomy and behavior, as well as the evolutionary history of modern humans.

Dutour has also been involved in archaeological excavations, particularly in the European context. His fieldwork has included the investigation of prehistoric sites, such as caves and open-air settlements, where he has uncovered and analyzed archaeological remains, including stone tools and animal remains.

Additionally, Dutour has explored the topic of ancient burial practices, studying the rituals and cultural significance associated with human burials throughout different periods of prehistory. His research has shed light on the social organization, religious beliefs, and mortuary practices of ancient societies.

Overall, Dutour's career has made significant contributions to our understanding of human evolution, prehistoric populations, and their interactions with their environments. His research has provided valuable insights into the behaviors, anatomical features, and cultural practices of ancient humans, enhancing our knowledge of our evolutionary past.

Dr Gerald Larrouy-Maumus is currently a Senior Lecturer in Molecular Microbiology from the Department of Life Sciences, Faculty of Natural Sciences at the Centre for Bacterial Resistance Biology, Imperial College London.
Dr Larrouy-Maumus did his undergraduate and master studies at Universite Paul Sabatier. From 2005-2009, Dr Larrouy-Maumus did his PhD at IPBS on the identification of the glycosyltransferases potentially involved in the biosynthesis of (lipo) polysaccharides found in the mycobacterial cell-envelope under the supervision of Dr Germain Puzo and Dr Jerome Nigou. From 2009-2011, Dr Larrouy-Maumus did his first post-doctoral training under the supervision of Dr Martine Gilleron still at the IPBS. Then, from 2011 until 2014, Dr Larrouy-Maumus did his second post-doctoral training, at MRC-NIMR London (UK), under the supervision of Dr Luiz de Carvalho, where he focused on the “functional annotation” of orphan enzymes in Mycobacterium tuberculosis using metabolomics.

In 2014, he secured a lectureship position at Imperial College London, where he established his laboratory. Over the last decade he has developed cutting edge expertise in biochemistry, lipidomics and metabolomics of bacterial pathogens.

In 2014, Dr Larrouy-Maumus secured a lectureship position at Imperial College London, where he established his laboratory. Over the last decade he has developed cutting edge expertise in biochemistry, lipidomics and metabolomics of bacterial pathogens. The major aims of the Larrouy-Maumus’ laboratory is to understand how mycobacterial metabolic flexibility impact drug resistance and immune persistence. In parallel, his lab is pioneering bacterial antibiotics susceptibility testing on intact bacteria using lipids for identification and read-out of AntiMicrobial Resistance using routine MALDI-ToF, the workhorse of clinical microbiology labs worldwide. That work has led, in 2022, to the commercialisation of a kit named MBT Lipid Xtract™ Kit (RUO) that allows the rapid detection, within 30 mins, of bacteria resistance to last resort antibiotics.

Gerald LARROUY-MAUMUS

Deciphering bacteria enviromental adaptation within the host

"Deciphering bacterial environmental adaptation within the host" refers to the study of how bacteria adapt and thrive within the unique environment provided by the host organism. When bacteria colonize the host, such as in human infections or symbiotic relationships, they encounter specific challenges and opportunities within the host's body.

Researchers in this field aim to understand the molecular mechanisms and genetic factors that allow bacteria to survive, proliferate, and establish themselves within the host environment. They investigate how bacteria interact with the host's immune system, evade immune responses, and manipulate host cell processes to their advantage.

The study of bacterial adaptation within the host involves examining various aspects, such as the bacterial virulence factors, host-pathogen interactions, microbial diversity, and the influence of the host's genetic and environmental factors on bacterial colonization and persistence.

Scientists use a range of techniques to decipher bacterial adaptation within the host, including genomic analysis, transcriptomics, proteomics, and metabolomics. These approaches help identify the genetic changes and expression patterns that contribute to bacterial survival and proliferation within the host.

Philippe FROGUEL

Genome structure anomalies in obesity

Throughout his career, Froguel has made significant contributions to the genetics of metabolic disorders. He has published numerous scientific papers and collaborated with researchers worldwide to advance our understanding of the genetic basis of conditions such as obesity, type 2 diabetes, and related metabolic disorders.

His work has involved the identification and characterization of genetic variants associated with these conditions, as well as the exploration of gene-environment interactions. Froguel has conducted large-scale genome-wide association studies (GWAS) to identify genetic loci associated with obesity and diabetes risk, shedding light on the complex genetic architecture of these diseases.

Froguel's research has not only contributed to our understanding of the genetic basis of metabolic disorders but also has implications for the development of personalized medicine approaches and strategies for disease prevention and treatment.

His publications often delve into the molecular mechanisms, gene-environment interactions, and genetic risk scores associated with obesity and diabetes. Froguel's research has shed light on the role of various genes and pathways in metabolic disorders and has contributed to our understanding of disease etiology, progression, and potential therapeutic targets.

Philippe Froguel, MD, PhD, works at Imperial College London as Prof and chair of Genomic Medicine, and at Lille University hospital as Prof of Endocrinology, where he is director of the Inserm/CNRSIPasteur/LilleUniv research group "Functional(epi)genomics and mechanisms of type 2 diabetes and related disorders”, Director of the European Genomic Institute for Diabetes research (EGID) and of the French National Center for Precision Medicine in diabetes PreciDIAB.

PF's scientific carrier is focused on the genetics of diabetes and obesity. He is author of 748 publications and his H-index is 178 (with 143K citations). PF has identified in 1992 the first diabetes gene (glucokinase), in 1998 the most prevalent cause of monogenic obesity (MC4R), and the first recessive mutation causing obesity in the leptin receptor gene. He discovered in 2006 the role of the sulfonylurea receptor gene ABCC8 in monogenic diabetes and in 2010-2011 the first evidence that Copy Number Variation causes extreme obesity or leanness depending of the quantity of DNA. He discovered in 2007 the first gene for common obesity (FTO) and has published in 2007 the first Genome Wide Association Study (GWAS) in T2D. Later, he found first gene frequent variants controlling glycemia (in GCPC2) and discovered the role of the melatonin pathway (through frequent and rare variants in MTNR1B) in T2D risk. Recently, he showed that 3% of patients with common T2D carry pathogenic mutations in actionable genes opening a path to precision medicine. PF current interest is in personalized medicine, with the identification of diabetic patients that should benefit from customized treatments controlling diabetes and preventing complications. The extension of this concept to diabetes renal and heart complications etc… may revolutionize diabetes care as rare deleterious mutations are present in every human but their clinical expression may be due to chronic hyperglycemia. To progress toward this direction PF have created the unique in France LIGAN Genome Sequencing Center.

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