B-cell genetic engineering for new therapeutic and vaccine modalities


Anne GALY – US 35
ART – Thérapie Génique (TG)

Key words

Gene Therapy
B lymphocytes
Gene editing
Infectious diseases

Key figures
  • Budget : 4,6 M€
  • Duration : 4 years (2023 – 2027)

B cells are important therapeutic targets that have yet to be harnessed for gene therapy. Exciting research results show the potential of genetically-engineered B cells for immunotherapy, vaccination or oncology.

THERA-B project assembles 6 partners expert in the fields of B cells, gene therapy, immunotherapy and vaccines to tackle the challenges of developing new therapeutic applications of genetically-engineered B cells and establish the processes for their bioproduction.

One of the possibilities is to engineer the B cell receptor or to reprogram the antigenic recognition of the B cells. B cells with re-programmed antigenic recognition will express and secrete neutralizing immunoglobulins that will be used to treat resistant infectious diseases (HIV, SARS-CoV-2, HBV) in combination with vaccination. This will generate new powerful modalities to neutralize the spread of infections or to eradicate viral reservoirs in the case of resistant chronic infections. Synthetic biology strategies will generate regulatable gene expression cassettes in B cells to achieve tunable systems that can provide on-demand anti-inflammatory effects in auto-immune disorders. In oncology and onco-hematology, complete remission could be achieved by enforcing the effects of immunotherapy with autologous engineered B-cells secreting biomedicines such as therapeutic antibodies.

All of these studies will rely on the development of efficient genetic engineering tools, performant cell culture systems and preclinical models including humanized mice and non-human primates.

Altogether, in 4 years, the THERA-B consortium has the ambition to establish a highly competitive expertise in B cell-immunotherapy in France. Through its associated structures including a LabEx focused on vaccines and two industrial integrators for biotherapy and bioproduction focused on gene therapy and RNAs, THERA-B aims to translate innovation into new clinically-applicable therapies.

Coordinating partner : Anne GALY – US 35
ART – Thérapie Génique (TG)
Michel COGNÉ – UMR 1236
EFS – Inserm – Rennes University
Microenvironment and B-cell: immunopathology cell differentiation and cancer (MOBIDIC)
Yves LÉVY – U955
Inserm – Paris Est Créteil University
Mondor Institute for Biomedical Research (IMRB)
François-Loïc COSSET – UMR 5308 – U1111
CNRS – ENS Lyon – Inserm – Claude Bernard Lyon 1 University
International Center for Infectiology Research (CIRI)
Infectious Diseases Models for Innovative Therapies (IDMIT)
Chantal PICHON – US55 ART-ARNm
Orléans University