Centre de Recherche sur l'Inflammation - UMRS 1139 INSERM (PARIS)
contact : P. MARTINEAU (IRCM-Inserm)
Assistant Professor Molecular Biology, Siriraj Hospital, Mahidol University (Thailand)
host: Emmanuel Cornillot (Montpellier University-IRCM)
Dr. Mutita Junking is an Assistant Professor of Molecular Biology within the
Research Department at the Faculty of Medicine, Siriraj Hospital, Mahidol
University. She also holds the position of Head of the Division of Molecular
Medicine in the Research Department and is the Deputy Director of the Siriraj
Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT).Her research focus on the advancing cellular immunotherapy for cancertreatment. Her research group has developed protocols and published data related to dendritic cell-induced anti-tumor T cells.They have also made
significant strides in developing chimeric antigen receptor (CAR) T cells
targeting tumor-associated antigens across various cancer models, including
hematologic malignancies and solid tumors. Dr. Mutita is dedicated to
pushing the boundaries in CAR T cell research, aspiring to create the next
generation of CAR T cells that are not only more effective but also hold
immense potential for treating cancer patients.
Résumé Séminaire :
Adoptive T cell therapy utilizing second-generation anti-CD19 chimeric
antigen receptor (anti-CD19-CAR2) T cells has achieved complete
remission in heavily pretreated patients with B cell acute lymphoblastic
leukemia (B-ALL) or diffuse large B cell lymphoma (DLBCL). However, the
clinical efficacy in aggressive B cell lymphomas (BCL) has been suboptimal
due to programmed cell death protein 1 ligand (PD-L1) expressed on BCL
cells binding to the PD-1 receptor on T cells, leading to limited T cell
function. We designed and generated anti-CD19-CAR4-T cells that secrete
anti-PD-L1 single-chain variable fragment (scFv), referred to as anti-CD19-
CAR5-T cells. Both anti-CD19-CAR-T cell types feature an anti-CD19 scFv
derived from monoclonal antibody, coupled with CD28/4-1BB/CD27/CD3ζ
f or enh anced f unc tion alit y. The ant i-PD-L1 scFv o rig in at es from
atezolizumab and demonstrated the ability to bind to PD-L1, inhibiting the
binding of anti-PD-L1 monoclonal antibodies to PD-L1high cancer cells. In
vitro evaluations showed that both anti-CD19-CAR4-T and anti-CD19-
CAR5-T cells efficiently targeted and killed CD19+ cancer cells in 2D and
3D co-culture systems. Interestingly, anti-CD19-CAR5-T cells displayed
superior proliferative capacity. At a low effector (E) to target (T) ratio of
0.5:1, anti-CD19-CAR5-T cells exhibited higher cytotoxicity against
CD19+/PD-L1high cells compared to anti-CD19-CAR4-T cells. Notably, the
cytotoxicity of anti-CD19-CAR4-T cells against CD19+/PD-L1high cells could
be restored by supplementing anti-PD-L1 scFv. Our findings highlight the
promising combination antitumor efficacy of anti-CD19-CAR4-T cells and
anti-PD-L1 scFv against CD19+/PD-L1high tumors. As a result, anti-CD19-
CAR5-T cells warrant further investigation in terms of in vivo antitumor
efficiency and potential inclusion in clinical trials as a treatment for
aggressive B cell lymphoma.
LiPiCS Services (Lyon-France)
contact : Eric JULIEN (CNRS/Inserm)
Protein-protein interactions are a key factor to understand a protein function. As we tried to identify molecular mechanisms explaining the pro and anti-tumoral effect of a well known transcription family, we developped a Bimolecular Fluorescence Complementation based asssay to screen in live cell line for whole interactome of a target. Reaching higher robustness than other screening technology, we performed comparative analysis to understand the effect of differents effectors and mutations on target interactome.
INTEGRAGEN, Genopole Campus, Evry (Paris)
contact : Pierre-François ROUX (equipe L. LeCam-INSERM)
Institut Pasteur, Department of Developmental and Stem Cell Biology
contact : Alexandre Djiane (IRCM)
Institut Pasteur, Department of Developmental and Stem Cell Biology
contact : Alexandre Djiane (IRCM)
INSERM U1280
Institute for Integrative Biology of the Cell (I2BC)
University Paris-Saclay-CEA-CNRS; Gif/Yvette
contact : Alexandre Djiane (Inserm-IRCM)
CNRS UMR 9019 Paris-Saclay
Intégrité du génome et cancer
Gustave Roussy, Villejuif
contact : Eric JULIEN (Inserm/CNRS)
Replication stress resulting from slowing or stalling of DNA replication forks is a major driver of genome instability during cancer initiation and progression. DNA replication can be challenged as a consequence of oncogene activation or by agents that interfere with DNA synthesis, such as the ones used in chemotherapy. To accomplish genome duplication and prevent chromosomal instability, cells have evolved mechanisms that protect, stabilize and/or restart replication forks while delaying cell cycle progression, which avoids entering mitosis with under-replicated DNA. Over the last years, however, work from several laboratories including ours has shown that cells can progress into mitosis with under-replicated DNA. This led to the identification of mechanisms, mediated by the Fanconi anemia (FA) and Homologous Recombination (HR) repair pathways, that promote post-replication repair and rescue of under-replicated DNA in mitosis, allowing cells to divide and continue proliferating. I will discuss how these findings have advanced our understanding of the link between replication stress and genome instability; I will present a molecular pathway that connects mitochondrial stress and functions of FA proteins in genome maintenance; finally, I will show that mechanisms involved in mitotic rescue of under-replicated DNA may represent promising targets to selectively kill cancer cells that sustain intrinsically high levels of replication stress.
Centre d'Immunologie de Marseille-Luminy (CMIL), CNRS-INSERM, Université Aix-Marseille
contact : Laurent Le Cam (Inserm)
Centro de Investigación del Cáncer (CIC) and Instituto de Biología Molecular y Celular del Cáncer (IBMCC), CSIC-USAL, Salamanca, Spain
contact : Antonio Maraver (Inserm) -ATTENTION Séminaire décalé au vendredi 02 Juin à 14h
KRAS oncogenes have been identified in a quarter of all human lung tumors. Recently, several inhibitors were developed that target specific mutant KRAS isoforms and two of them, directed against the KRAS G12C oncoprotein, have just been approved. However, most patients develop resistance against these inhibitors and no actual survival benefits have been observed in clinical trials. Thus, it is urgently required to identify novel therapeutic options applicable to most if not all patients with KRAS-mutant tumors. I will discuss what we have learned from genetically engineered mouse models about the development of resistance to KRAS inhibition. Moreover, I will present novel insights into the mechanisms of KRAS signaling in lung cancer and how a better understanding of KRAS signaling may help to overcome resistance to targeting either KRAS itself or its MAPK effector pathway.
Centre de Recherche des Cordeliers, INSERM UMRS1138, Paris
contact : Florence Cammas (Inserm/CNRS)
Vizgen, MEng, MBA, Regional Account Manager
contact : Laurent Le Cam (Inserm)
Biological systems are composed of numerous cell types, intricately organized to form functional tissues and organs. While recent advancements in genomics technologies have made it possible to characterize cell types through careful analysis of the transcriptome, they are unable to resolve how gene expression and cell types are spatially arranged. In this presentation, we introduce you to Vizgen’s all-in-one in situ genomics platform MERSCOPE, which enables the direct profiling of the spatial organization of intact tissue with genomic scale
throughput. The instrument, the MERFISH chemistry and use cases will be presented as well.
Located in the Parc Euromédecine, the Institut de Recherche en Cancérologie de Montpellier (U1194) is located on the Val d'Aurelle Campus (ICM, Institut régional du Cancer Montpellier/ Val d'Aurelle).
U1194 Research Centre supported by Inserm, the University of Montpellier and the Institut du Cancer de Montpellier (ICM)
Institut de Recherche en Cancérologie de