A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.

The present invention relates to a TCR or functional variant thereof having antigenic specificity for CD1c molecules associated with a self-lipid, preferably (mLPA) or derivative thereof, to relative polypeptide, protein, nucleic acid, recombinant expression vector, host cell, population of cells, antibody and pharmaceutical composition. The present invention also relates to the uses of said TCR and relative products, in particular for use in the treatment and/or prevention of an hematological disorder.

The present invention relates to a TCR or functional variant thereof having antigenic specificity for CD1c molecules associated with a self-lipid, preferably (mLPA) or derivative thereof, to relative polypeptide, protein, nucleic acid, recombinant expression vector, host cell, population of cells, antibody and pharmaceutical composition. The present invention also relates to the uses of said TCR and relative products, in particular for use in the treatment and/or prevention of an hematological disorder.

The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells. Depletion of CD8+ T cells from the donor lymphocyte infusion reduces the risk of sustained engraftment and graft-versus-host disease. Removal of regulatory T cells from the infused population may augment the ability of non-regulatory T cells to provide help for endogenous effectors of anti-tumor immunity. Allogeneic T cell therapy is typically given in the context of allogeneic stem cell transplantation, in which the patient receives highly immunosuppressive conditioning followed by an infusion of a stem cell graft containing unselected populations of mature T cells. In the treatment described here, the graft is engineered to minimize the possibility of sustained donor cell engraftment, and the anti-tumor effector T cells derive from the host.

The disclosure relates to delivery systems, and corresponding methods, for selecting and delivering an allogeneic T-cell line for administration to a patient, e.g., according to the HLA profile of the patient's somatic or diseased cells.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

Embodiments of the disclosure include methods and compositions for immunotherapy that comprise allogeneic cells that are able to be universally tolerated in host individuals. In specific embodiments the cells have reduced expression of endogenous beta2-microglobulin (B2M) and/or MHC class II-associated invariant chain (Ii), and in particular cases the cells are NKT cells that lack the ability to damage host tissues, have much reduced recognition by host immune cells, and surprisingly avoid destruction by host NK cells. In some embodiments, B2M- and/or Ii-targeting molecules are engineered to be expressed in combination (including within a single construct) with recombinantly engineered receptors, for example, for a one-hit generation of universally tolerated off-the-shelf immunotherapy.

Described are methods for the production and use of cryopreservable double negative T cells (DNTs) for the treatment of cancer as an off-the-shelf cellular therapy. A sample population of DNTs is expanded using DNTs from one or more donors. The expanded population of DNTs from different donors does not exhibit alloreactivity against allogenic cells in the expanded population. The expanded populations of DNTs can be long-term stored as cryopreserved products.

Systems, compositions, and methods are described that utilize three dimensional tumor models incorporating tissue barrier (such as a stromal barrier) around tumor cells in culture, which permit replication in vivo immune cell response to tumor cells. Such tumor models are used to accurately assess appropriate therapeutic modes and protocols that are likely to be effective against the individual's tumor. Such tumor models can be used to selectively expand immune cells that are responsive to tumor cells utilized in the model. Such an expanded population of immune cells can subsequently be utilized therapeutically.

Systems, compositions, and methods are described that utilize three dimensional tumor models incorporating tissue barrier (such as a stromal barrier) around tumor cells in culture, which permit replication in vivo immune cell response to tumor cells. Such tumor models are used to accurately assess appropriate therapeutic modes and protocols that are likely to be effective against the individual's tumor. Such tumor models can be used to selectively expand immune cells that are responsive to tumor cells utilized in the model. Such an expanded population of immune cells can subsequently be utilized therapeutically.