Publications by Alexandre Harari

Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes

Florence Pojer, George Coukos, Kelvin Ka Ching Lau, Amédé Noredine Larabi, Julien Racle, David Gfeller, Philippe Guillaume Coune, Marta Andreia Da Silva Perez, Alexandre Harari

CD4+T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on class II major histocompatibility complex (MHC-II) molecules. The high polymorphism of MHC-II genes represents an important hurdle toward ...

CELL PRESS2023

Microfluidic T Cell Selection by Cellular Avidity

Li Tang, Armand Kurum, Alexandre Harari

No T cell receptor (TCR) T cell therapies have obtained clinical approval. The lack of strategies capable of selecting and recovering potent T cell candidates may be a contributor to this. Existing protocols for selecting TCR T cell clones for cell therapi ...

WILEY2022

Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING

Julien Dorier, George Coukos, Christian Iseli, Mauro Delorenzi, Alizée Jéléna Grimm, Giovanni Ciriello, Alexandre Harari, Marco Mina

In this study, we investigate mechanisms leading to inflammation and immunoreactivity in ovarian tumors with homologous recombination deficiency (HRD). BRCA1 loss is found to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammat ...

2021

Microfluidic Device for Droplet Pairing by Combining Droplet Railing and Floating Trap Arrays

Philippe Renaud, Margaux Catherine Marie Duchamp, George Coukos, Alexandre Harari, Marion Arnaud

Droplet microfluidics are characterized by the generation and manipulation of discrete volumes of solutions, generated with the use of immiscible phases. Those droplets can then be controlled, transported, analyzed or their content modified. In this wide d ...

MDPI2021

Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer

George Coukos, Florian Huber, Stéphanie Tissot, Johanna Pauline Chiffelle, Alexandre Harari

T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specifi ...

2021

Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer

Hatice Altug, Alexander Mathis, George Coukos, Xiaokang Li, Yen-Cheng Liu, David Gfeller, Pedro Romero, Alexandre Harari, Amélie Cachot, Margaux Saillard

CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displayi ...

2021

Unsupervised Analysis of Flow Cytometry Data in a Clinical Setting Captures Cell Diversity and Allows Population Discovery

Nicolas Jean Philippe Guex, George Coukos, Fabrizio Benedetti, Ioannis Xenarios, Alexandre Harari

2021

Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes

Didier Trono, George Coukos, Marion Leleu, Evaristo Jose Planet Letschert, Markus Müller, Florian Huber, Laia Simo Riudalbas, Delphine Yvette L Grun, Ioannis Xenarios, Lin Zhang

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides derived from annotated ...

Nature Research2020

Biotechnologies to tackle the challenge of neoantigen identification

Philippe Renaud, Margaux Catherine Marie Duchamp, George Coukos, Alexandre Harari, Marion Arnaud

Among immune correlates of clinical responses, tumor-specificneoantigens took the spotlight as relevant targets for cancerimmunotherapy. The implementation of pipelines forpersonalized cancer therapy remains challenging due to theprivacy, that is patient-s ...

2020

Tumor-Specific Cytolytic Cd4 T Cells Mediate Protective Immunity Against Human Cancer

Hatice Altug, Alexander Mathis, Xiaokang Li, George Coukos, Yen-Cheng Liu, David Gfeller, Pedro Romero, Alexandre Harari, Amélie Cachot, Margaux Saillard

BMJ PUBLISHING GROUP2020