Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

The present invention relates to a chimeric antigen receptor (CAR) comprising an extracellular domain that binds to one or more inflammation associated factor(s), a transmembrane/hinge domain and an intracellular domain. In a specific embodiment, a T regulatory (Treg) cell expressing a construct encoding said CAR which further comprising a Fox3p and a CAR activation-dependent NF-AT promoter that drives the expression of interleukin-10 and TGF-beta. It also relate to the methods of producing the CAR, the Treg cells expressing said CAR and the use of said CAR to treat autoimmune diseases such as transplant rejection, a graft versus host disease (GVHD) and cytokine release syndrome..

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

Embodiments of the present disclosure relate to compositions and methods of enhancing anti-tumor activities of modified cells, the method comprising: administering an effective amount of the modified cells to a subject having a solid tumor; and administering an effective amount of an agent to the subject, the agent comprising rapamycin, wherein the modified cells inhibit growth of the solid tumor in the subject, and wherein the anti-tumor activities in the subject are greater than those in a subject that is administered with an effective amount of modified cells but without the agent.

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

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.