Tuesday, 21 January 2020, 12h00 MSG-025 Bernal Institute
Immunotherapy in Oncology and Addressing the Challenges with Combination Strategies
Immune checkpoint blockade (ICB) therapies, such as the ones targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or programmed cell death protein 1 (PD-1), have displayed durable clinical responses in various cancers and are now approved by the FDA for a growing list of cancer types. Although these new immunotherapies have had a notable effect on cancer treatment, they only benefit a limited subset of patients, and multiple mechanisms of acquired immune resistance have been described. Tumours considered immunologically “cold”, with reduced or even absent infiltration of T-cells, are a major hurdle in the cancer immunotherapy field, and strategies to overcome this resistance mechanism constitute an unmet need. Recent efforts have focused on combining this immunotherapy approach with other therapies to maximize its potential. However, the candidate for these combination therapies are numerous and therefore the need for mechanism based and rationally designed therapies is needed. Our approach to studying the molecular determinants of checkpoint-blockade clinical activity will be outlined during this presentation. Our ongoing strategies to select and develop proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization will also be presented.
ABOUT THE PRESENTER
Dr Merghoub received a BA degree in Genetics from University of Algiers, Algeria, a MSc in Applied Biology and Genetics and a PhD in Human Genetics from The University of Paris 7, France. He pursued his post-doctoral research with Dr Pier Paolo Pandolfi at Memorial Sloan Kettering Cancer Center (MSK) in New York, USA. He characterized the transcriptional properties of the Pokemon gene and its role during development which led to publications in Nature and Science. Dr Merghoub was a Senior Research Scientist in Dr Alan Houghton’s laboratory from 2002-2008. His research focus included development of mouse models that spontaneously develop melanoma, elucidating the interactions between tumors and the immune system, and examining the role of FAP (fibroblast activation protein-alpha) in tumorigenesis. Since 2008, Dr Merghoub acts as principle investigator and is now an Attending Lab Member at MSK. He researches the pathogenesis and treatment of melanoma, and develops tools to study melanoma as model system. The majority of Merghoub’s research uses mice to test the interactions of solid tumors with various components of the immune system. He is developing mouse models of melanoma that mimic different stages of human disease clinically, pathologically and genetically, later evaluating new immunotherapies at different stages of tumor progression in experiments. He is also generating mice whose immune cells are genetically labelled with fluorescent proteins that allow him to track the in vivo behavior of specific immune cells in a melanoma-bearing host. His research is heavily translational and aims to design means to overcome resistance to immune checkpoint blockade, and defining biomarkers and genetic determinants of response to immune therapy.
Dr Merghoub’s findings have been published in top-tier journals including Science, Nature, Nature Medicine, Nature Immunology, Cancer Cell. He has a h-index of 50 and over 17250 citations.