Abstract: The invention pertains to the field of adoptive cell immunotherapy. It provides with engineered immune cells comprising genetic alteration into genes which are involved into immune functions downregulation, especially in response to environment signals such as nutrients depletion. Such method allows the production of more potent immune cells in the context of tumors' microenvironment.

Abstract: The present invention relates to new CD22 Chimeric Antigen Receptors (CD22 CAR), an engineered immune cell endowed with said new CD22 CAR and comprising at least inactivated TRAC gene for use in therapy. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Abstract: The invention relates to the fields of immunotherapy, molecular biology and recombinant nucleic acid technology. In particular, the invention relates to a TALEN-modified human primary cell comprising in its genome, a modified human T cell receptor alpha gene with an insertion comprising at least, from 5? to 3?, a polynucleotide encoding a self-cleaving peptide, a chimeric antigen receptor, wherein the cell has undetectable cell-surface expression of the endogenous alpha beta T cell receptor as compared to a TCR positive control cell and expresses a receptor to target a pathological cell, use of said cell for treating a disease, including cancer. The invention further relates to methods for producing such a TALEN-modified cell, and to means for detecting such an engineered human primary cell or other genetically modified human primary cell obtained using alternative and/or additional rare cutting endonucleases.

Abstract: The invention pertains to the field of adoptive cell immunotherapy. It provides with engineered immune cells comprising genetic alteration into genes which are involved into immune functions downregulation, especially in response to environment signals such as nutrients depletion. Such method allows the production of more potent immune cells in the context of tumors' microenvironment.

Abstract: The present invention relates to new CD22 Chimeric Antigen Receptors (CD22 CAR), an engineered immune cell endowed with said new CD22 CAR and comprising at least inactivated TRAC gene for use in therapy. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Abstract: The present disclosure provides in vitro and in vivo methods for selecting a candidate CAR polynucleotide to be expressed in immune cells for its preferential capability to make immune cells proliferate in an antigen-dependent manner.

Abstract: The present invention relates to gene editing methods to engineer primary immune cells that are made resistant to proteasome inhibitors, such as Bortezomib, Carfilzomib, Ixazomib, Marizomib, Delanzomib or Oporozomib, for their use in cell immunotherapy in combination with proteasome inhibitor treatments.