Hematopoeitic stem/progenitor cells (HSPC) and/or non-T effector cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to activate, promote proliferation of, detect, enrich, isolate, track, deplete and/or eliminate modified cells. The cells can also be modified to express a binding domain.

The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising disrupted T cell receptor and/or HLA and comprising a chimeric antigen receptor. In certain embodiments, the compositions are employed allogeneically as universal reagents for “off-the-shelf” treatment of medical conditions such as cancer, autoimmunity, and infection. In particular embodiments, the T cell receptor-negative and/or HLA-negative T cells are generated using zinc finger nucleases, for example.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The present disclosure provides ex vivo armed T cell (EAT) compositions that comprise multi-specific (e.g., bispecific) antibodies that bind to CDS and at least one additional target antigen (e.g., antigen that is expressed by tumor cells and/or a DOTA label). The EAT compositions of the present technology are useful for adoptive immunotherapy in a subject in need thereof.

The present disclosure provides ex vivo armed T cell (EAT) compositions that comprise multi-specific (e.g., bispecific) antibodies that bind to CDS and at least one additional target antigen (e.g., antigen that is expressed by tumor cells and/or a DOTA label). The EAT compositions of the present technology are useful for adoptive immunotherapy in a subject in need thereof.

There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

The present invention provides a method for treating a solid cancer which comprises the step of administering a cell to a subject, wherein the cell comprises a nucleic acid sequence encoding interleukin 12 (IL-12) downstream of a frame-slip motif (FSM) or a translational readthrough motif (TRM).

Provided herein are chimeric antigen receptors (CARs) comprising an antigen binding domain (e.g., CD19, CD30, GD2, etc.), transmembrane domain (e.g., CD28), and a cytoplasmic domain (e.g., CD27, 4-1BB, etc.). In some aspects, the disclosure relates to use of the CARs in T cells, compositions, kits and methods.

Provided herein are methods for delaying or inhibiting T cell maturation or differentiation in vitro for a T cell therapy, comprising contacting one or more T cells from a subject in need of a T cell therapy with an AKT inhibitor and at least one of exogenous Interleukin-7 (IL-7) and exogenous Interleukin-15 (IL-15), wherein the resulting T cells exhibit delayed maturation or differentiation. In some embodiments, the method further comprises administering the one or more T cells to a subject in need of a T cell therapy.

A vaccine composition for enhancing in a subject to whom the composition is administered, a production of antibodies against a disialoganglioside GD3 and/or GD2 is provided in one embodiment. The composition includes, in an embodiment, a liposome including an effective amount of disialoganglioside GD3 and/or GD2 to stimulate or enhance antibody production in the subject; and an effective amount of an adjuvant comprising monophosphory 1 lipid A (MPL). In one example, the vaccine composition may be administered to the subject in conjunction with a chemotherapy.