Provided herein are compositions and methods for the treatment of cancers using modified TILs, wherein the modified TILs include one or more immunomodulatory agents (e.g., cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and/or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

The present application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, NKG2D CAR expressing cells that also express IL-18 are proposed. Also proposed are polynucleotides, vectors encoding the NKG2D CAR and IL-18 and cells expressing both. These cells are particularly suitable for use in immunotherapy, including allogeneic therapy. The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. Further, strategies to treat diseases such as cancer using these cells are also provided. The engineered immune cells, such as T-cells or natural killer (NK) cells, expressing such CARs are suitable for treating lymphomas, multiple myeloma and leukemia, but other tumors can be treated as well, depending on the specificity of the CAR. Most notably, as expression and secretion of the pro-inflammatory cytokine IL-18 is beneficial to reducing the immunosuppressive effect of the tumor microenvironment, treatment of solid tumors is envisaged.

Provided herein are, inter alia, compositions comprising chimeric antigen receptor (CAR)-engineered immune cells, methods of formulating, and methods useful for treating cancer and leukemia.

Disclosed are nucleic acids and polypeptides which provide the co-expression of interleukin (IL)-21 and IL-15 by a host cell, each interleukin being bound to the cell membrane by a cell membrane anchor moiety. Also disclosed are related recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

The present disclosure relates to IL2 agonists with improved therapeutic profiles.