Use of the cd2 signaling domain in second-generation chimeric antigen receptors

An isolated chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the costimulatory signaling region comprises the CD2 signaling domain

A cell comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), the CAR comprising an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the costimulatory signaling domain comprises the CD2 signaling domain.

A vector comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the costimulatory signaling region comprises the CD2 signaling domain.

A method for stimulating a T cell-mediated immune response to a target cell population or tissue in a mammal, the method comprising administering to a mammal an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising the CD2 signaling domain, and a CD3 zeta signaling domain, and wherein the antigen binding domain is selected to specifically recognize the target cell population or tissue.

A method of providing an anti-tumor immunity in a mammal, the method comprising administering to the mammal an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising the CD2 signaling domain, and a CD3 zeta signaling, thereby providing an anti-tumor immunity in the mammal.

A method of treating a mammal having a disease, disorder or condition associated with an elevated expression of a tumor antigen, the method comprising administering to the mammal an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain a transmembrane domain, a costimulatory signaling region comprising the CD2 signaling domain, and a CD3 zeta signaling domain, thereby treating the mammal.

A method of treating a human with cancer, the method comprising administering to the human a T cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising the CD2 signaling domain, and a CD3 zeta signaling domain.

A method of generating a persisting population of genetically engineered T cells in a human diagnosed with cancer, the method comprising administering to the human a T cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain a transmembrane domain, a costimulatory signaling region comprising the CD2 signaling domain, and a CD3 zeta signaling domain, wherein the persisting population of genetically engineered T cells persists in the human for at least one month after administration.

A method of expanding a population of genetically engineered T cells in a human diagnosed with cancer, the method comprising administering to the human a T cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising the CD2 signaling domain, and a CD3 zeta signaling domain, wherein the administered genetically engineered T cell produces a population of progeny T cells in the human.

A method of modulating the amount of cytokine secreted by a T cell, said method comprising genetically engineering the T cell to express a CAR, wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory domain region comprising CD2, and a CD3 zeta signaling domain.

A method of reducing the amount of activation-induced calcium influx into a T cell, said method comprising genetically engineering the T cell to express a CAR, wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory domain region comprising CD2, and a CD3 zeta signaling domain.