Actualités
Séminaires

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.

Mutita JUNKING, PhD

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.

Elodie LALLET

INTEGRAGEN, Genopole Campus, Evry (Paris)

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

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