The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Provided herein are ex vivo methods for expanding regulatory T cells (Tregs), including engineered Tregs, while maintaining their stability and activity. In addition to improving growth and expansion of Tregs, the methods, which can comprise the use of discontinuous stimulation of regulatory T cells (DSORT?), produce Tregs with increased stability and activity.

The present invention relates to a method for producing antigen-specific T cells and their use in a method for the treatment or prevention of cancer.

The present disclosure relates to T cells engineered to comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG, a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA, and insertion of sequence(s) encoding a regulatory T cell promoting molecule and compositions and uses thereof.

The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Hyper-lgE syndrome (HIES). In particular, the present invention provides means and methods for genetically modifying HSCs or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides populations of engineered HSCs or T-cells which comprise cells comprising an exogenous polynucleotide sequence comprising at least a partial or complete sequence of a functional STATS gene, said exogenous polynucleotide sequence being integrated in an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), resulting in the expression of a functional STATS polypeptide. The present invention further provides pharmaceutical compositions comprising the cell populations of the invention, and their use in gene therapy for the treatment of Hyper-lgE syndrome (HIES).

In some embodiments, the present disclosure pertains to a method of enhancing chimeric antigen receptor expressing T cell function. In some embodiments, the method comprises activating the chimeric antigen receptor expressing T cells. In some embodiments, the method further comprises determining the differential expression of at least one molecule on the chimeric antigen receptor T cells. In some embodiments, the method comprises targeting the at least one molecule. In some embodiments, the present disclosure pertains to a method of treating a tumor in a subject in need thereof. In some embodiments, the method comprises administering to the subject an infusion of chimeric antigen receptor expressing T cells. In some embodiments, the method further comprises determining the differential expression of at least one molecule on the chimeric antigen receptor T cells. In some embodiments, the method comprises targeting the at least one molecule, wherein the molecule is differentially expressed upon activation of the chimeric antigen receptor expressing T cells.

The present invention relates to a composition for priming a human Natural Killer (NK) cell. The present invention provides a natural killer (NK) cell priming composition which comprises (i) a CD2 ligation agent; (ii) an NKp46 ligation agent; and (iii) an LFA-1 ligation agent. The present invention also provides an NK-cell priming substrate which comprises (i) a CD2 ligation agent; (ii) an NKp46 ligation agent; and (iii) an LFA-1 ligation agent.

The present invention relates to methods and compositions for treating autoimmune or inflammatory disease characterised by an aberrant or inappropriate immune response to one or more of Ro60 protein; MPO protein; and Smith protein.

The present disclosure provides chimeric antigen receptor polypeptides having antigen recognition domains for CD2, CD3, CD4, CD5, CD7, CD8, and CD52 antigens, and polynucleotides encoding for the same. The present disclosure also provides for engineered cells expressing the polynucleotide or polypeptides. In some embodiments, the disclosure provides methods for treating diseases associated with CD2, CD3, CD4, CD5, CD7, CD8, and CD52 antigens.

Methods of producing a mitochondria extract comprising providing primary human hematopoietic cells in suspension, expanding the primary human hematopoietic cells, and isolating mitochondria are provided. Mitochondria extracts, compositions comprising mitochondria extract and methods of use of the extracts and compositions are also provided.