An engineered immune cell, which expresses (i) a cell surface molecule that specifically recognizes a ligand, (ii) an exogenous interleukin, and (iii) an exogenous Flt3L, XCL2, and/or XCL1; the engineered immune cell can be used for treating cancer, infection, or autoimmune diseases; and compared with a traditional engineered immune cell, the engineered immune cell has significantly improved tumor killing activity.

Provided herein are targeted cytokine constructs and method of engineered cell therapy by administering a targeted cytokine construct in combination with an engineered cell therapy, for use in treating a disease, e.g., a proliferative disease, e.g., a cancer.

The present disclosure provides, among other things, a method for efficiently producing a cell population enriched in Natural Killer cells (NK cells) from induced pluripotent cells.

Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.

The disclosure relates to immune cells comprising one or more vectors comprising a nucleic acid sequence encoding a chimeric antigen receptor specific for CD19 and a nucleic acid sequence encoding an enhancer of T cell priming (e.g., IL-18), compositions comprising the T cells, and methods of generating and/or using the T cells to treat diseases associated with the expression of CD19.

The invention provides a natural killer (NK) cell engineered to express a chimeric antigen receptor (CAR), wherein the CAR comprises the extracellular domain of CD27 or a CD70-binding portion thereof, as well as compositions comprising the engineered NK cell, methods for producing the engineered NK cell, and therapeutic applications of the engineered NK cell, such as for treating neoplastic diseases.

An object of the present invention is to provide CAR-expressing T cells that coexpress a chimeric antigen receptor (CAR) and a T cell immune function-enhancing factor and have a high immunity-inducing effect and antitumor activity, and to provide a CAR expression vector for the preparation of the CAR-expressing T cells.

A CAR expression vector comprises a nucleic acid encoding a chimeric antigen receptor (CAR) and a nucleic acid encoding a T cell immune function-enhancing factor, wherein the nucleic acid encoding an immune function-enhancing factor is a nucleic acid encoding interleukin-7 and a nucleic acid encoding CCL19, a nucleic acid encoding a dominant negative mutant of SHP-1, or a nucleic acid encoding a dominant negative mutant of SHP-2, or a CAR-expressing T cell introduced with the CAR expression vector are prepared.

The invention involves the discovery that if dendritic cells loaded with a tumor antigen are cultured in interleukin-15 (IL-15), or if T cells activated by the dendritic cells are cultured in IL-15, Treg activity that is specific for the tumor antigen is reduced. This reduction in Treg activity results in an increase in anti-tumor immune response. Another embodiment of the invention involves the discovery that incubating dendritic cells with a MAP kinase inhibitor in combination with IL-15 gives synergistic benefits when the dendritic cells are used to activate T cells. Dendritic cell and T cell compositions incubated with IL-15 or a MAP kinase inhibitor are provided.

This disclosure describes chimeric antigen receptors (CARs) engineered immune cells including the CARs, pharmaceutical compositions that include engineered immune cells that include the CARs, and methods involving such engineered immune cells.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.