The invention provides methods of depleting CD5+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD5 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.

The present disclosure provides methods of increasing the activity of regulatory T cells (Tregs), e.g., to treat autoimmune or inflammatory diseases or disorders, using antagonist, nondepleting antibodies and antigen-binding fragments thereof that specifically bind to OX40 (e.g., human OX40).

The present invention provides compositions and methods for expanding natural T regulatory cells (nTregs) without substantially sacrificing suppressive function of the cells. Accordingly, the invention provides uses of the expanded nTregs for cellular therapy.

A methodology to obtain in vitro large numbers of human induced regulatory T cells with specificity to the donor antigen, with a phenotype and stable suppressor function in the presence of pro-inflammatory cytokines, through of co-cultures of monocyte-derived dendritic cells and T cells na?ve, both from genetically unrelated individuals (donor and recipient) is disclosed. The cells obtained with the present method are of CD4, CD25, CTLA-4 and FOXP3+ phenotype and show a specific suppressor function on donor antigen-specific T lymphocytes. These cells maintain their phenotype and stable suppressive function in presence of pro-inflammatory cytokines TNF-? and IL-6. The stability and the number obtained make them candidates as therapeutic tools for transplantation.

The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem/progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem/progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of na?ve conventional ??-T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.

The invention includes compositions comprising at least one chimeric alloantigen receptor (CALLAR) specific for an alloantibody, vectors comprising the same, compositions comprising CALLAR vectors packaged in viral particles, and recombinant T cells comprising the CALLAR. The invention also includes methods of making a genetically modified T cell expressing a CALLAR, wherein the expressed CALLAR comprises a Factor VIII or fragment thereof extracellular domain.

The invention relates to a composition comprising regulatory T (Treg) cells or effector T cells (Teff) which stably express an interleukin selected from the group consisting of interleukin-2 (IL-2) or interleukin-15 (IL-15).

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

The present disclosure relates to the acceleration of hematopoietic compartment reconstitution in a subject in need of hematopoietic stem cell transplantation by administering a composition having a protein transduction domain-MYC (PTD-MYC) fusion protein in combination with hematopoietic stem cell transplantation and to the enhancement of hematopoietic compartment autoreconstitution in a subject in need thereof by administering a composition having a protein transduction domain-MYC (PTD-MYC) fusion protein.

The invention relates to a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135?45? to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g. Furthermore, the invention relates to a method for modifying cells comprising the steps introducing cells in a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135?45? to the rotational axis of the centrifugation chamber wherein and comprising at least one input/output port, immobilizing the cells on the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g maintaining the rotation of the rotation of the centrifugation chamber until the cells are modified.