The present invention provides use of an agent that inhibits EP4 activity and an immuno-oncology agent, or a composition thereof, for treatment of a cancer.

The present invention provides use of an agent that inhibits EP4 activity and an immuno-oncology agent, or a composition thereof, for treatment of a cancer.

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.

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.

Embodiments of the disclosure concern methods and compositions related to cancer therapy using myeloid derived suppressor cells (MDSC) as a solo therapy or an adjunct therapy. The MDSCs are prepared by exposing bone marrow cells or blood cells to one or more compositions that induce their differentiation to MDSCs and also to TGF-β1, and in specific embodiments the exposure to TGF-β1 results in the MDSCs having anti-tumor activity and/or immune stimulatory activity.

Embodiments of the disclosure concern methods and compositions related to cancer therapy using myeloid derived suppressor cells (MDSC) as a solo therapy or an adjunct therapy. The MDSCs are prepared by exposing bone marrow cells or blood cells to one or more compositions that induce their differentiation to MDSCs and also to TGF-β1, and in specific embodiments the exposure to TGF-β1 results in the MDSCs having anti-tumor activity and/or immune stimulatory activity.

As disclosed herein, stromal cells are important for the recruitment and organization of lymphocytes in TLSs. Therefore, disclosed herein are composition and methods for bioengineering TLSs in animals, such as mice. These compositions involve chemokine-releasing microparticles or cells that can be implanted into the animals. Therefore, disclosed herein are chitosan hydrogels with chemokine releasing microparticles or cells.

As disclosed herein, stromal cells are important for the recruitment and organization of lymphocytes in TLSs. Therefore, disclosed herein are composition and methods for bioengineering TLSs in animals, such as mice. These compositions involve chemokine-releasing microparticles or cells that can be implanted into the animals. Therefore, disclosed herein are chitosan hydrogels with chemokine releasing microparticles or cells.

As disclosed herein, stromal cells are important for the recruitment and organization of lymphocytes in TLSs. Therefore, disclosed herein are composition and methods for bioengineering TLSs in animals, such as mice. These compositions involve chemokine-releasing microparticles or cells that can be implanted into the animals. Therefore, disclosed herein are chitosan hydrogels with chemokine releasing microparticles or cells.

Compounds having the following Formula I and/or Formula II and methods of their use and preparation are disclosed: ##STR00001##