Mercredi 08 Novembre 2023 de 11h00 à 12h15
SEMINAIRE Labex MabImprove

Docteur Renaud LESOURNE

Institut Toulousain des Maladies Infectieuses et Inflammatoires

" Signaling modulation of immune checkpoints in T cells in normal and autoimmune contexts "

contact : M.A. Poul (IRCM)

Jeudi 09 Novembre 2023 de 14h00 à 15h00

Vanja Sisirak

CNRS Research Scientist (CRCN)
Immuno-ConcEpT Team, CNRS UMR 5164

"Role of DNASEs in the regulation of self DNA immunostimmulatory potential in health and disease”

contacts : Julien Faget ou Marie-Alix Poul ou Julie Constanzo (IRCM)

Jeudi 05 Octobre 2023 de 14h00 à 15h15


Assistant Professor Molecular Biology, Siriraj Hospital, Mahidol University (Thailand)

Chimeric Antigen Receptor T Cells Targeting CD19 and Secreting Anti-PD-L1 Single Chain Variable Fragment Reduce PD-L1-induced T Cell Exhaustion

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.


Vendredi 29 Septembre 2023 à 14h00

Jonathan Reboulet

LiPiCS Services (Lyon-France)

"Application of a  new protein-protein interactions screening technology to decipher oncoprotein interactomes and their alterations by mutations, drugs and peptides."

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.

Vendredi 10 Novembre 2023 de 14h00 à 16h00


INTEGRAGEN, Genopole Campus, Evry (Paris)

"Innovation en analyses et tests Génomiques : nouvelles avancées en oncologie"

contact : Pierre-François ROUX (equipe L. LeCam-INSERM)

Mardi 12 Septembre 2023 de 11h00 à 12h30


Institut Pasteur, Department of Developmental and Stem Cell Biology

Toward a predictive understanding of epithelial cell death

contact : Alexandre Djiane (IRCM)


Institut Pasteur, Department of Developmental and Stem Cell Biology

Toward a predictive understanding of epithelial cell death

contact : Alexandre Djiane (IRCM)

Mardi 04 Juillet 2023 de 14h00 à 15h00

Katarzyna SIUDEJA


Institute for Integrative Biology of the Cell (I2BC)

University Paris-Saclay-CEA-CNRS; Gif/Yvette

Endogenous retroviral activity in the fly intestine - towards the mechanisms of action of selfish DNA in the soma

contact : Alexandre Djiane (Inserm-IRCM)




Vendredi 16 Juin 2023 de 14h00 à 15h00
SEMINAIRE IRCM Vendredi 16 juin

Valéria NAIM

CNRS UMR 9019 Paris-Saclay

Intégrité du génome et cancer

Gustave Roussy, Villejuif

"Understanding genome instability from S-phase to mitosis"

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.

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