Compositions and methods for immunotherapy

A method of inducing tumor cell death in a tumor, the method comprising contacting said tumor cell with an immunoresponsive cell comprising an antigen recognizing receptor that binds a first tumor antigen with low affinity, wherein the binding activates the immunoresponsive cell, and a chimeric co-stimulating receptor (CCR) that binds a second tumor antigen and stimulates the immunoresponsive cell, thereby inducing tumor cell death in said tumor.

A method of treating or preventing a neoplasia in a subject, the method comprising administering an effective amount of an immunoresponsive cell comprising an antigen recognizing receptor that binds a first antigen with low affinity, wherein the binding activates the immunoresponsive cell, and a chimeric co-stimulating receptor (CCR) that binds a second antigen and stimulates the immunoresponsive cell, thereby treating or preventing a neoplasia in the subject.

A method of inducing tumor cell death, the method comprising administering an effective amount of an immunoresponsive cell comprising an antigen recognizing receptor that binds a first antigen with low affinity, wherein the binding activates the immunoresponsive cell, and a chimeric co-stimulating receptor (CCR) that binds a second antigen and stimulates the immunoresponsive cell, thereby inducing tumor cell death in the subject.

A method for producing an antigen-specific immunoresponsive cell, the method comprising introducing into the immunoresponsive cell a nucleic acid sequence that encodes a chimeric co-stimulating receptor (CCR), wherein the chimeric co-stimulating receptor comprises an antigen-binding domain coupled to an intracellular signaling domain that stimulates an immunoresponsive cell, wherein the immunoresponsive cell comprises an antigen recognizing receptor that binds a first antigen with low affinity, wherein the binding activates the immunoresponsive cell.

A method of treating prostate cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a T cell comprising an antigen recognizing receptor that binds PSCA or CD19 with low affinity, wherein the binding activates the immunoresponsive cell, and a chimeric co-stimulating receptor (CCR) that binds PSMA and stimulates the immunoresponsive cell, thereby treating prostate cancer in the subject.

A T cell comprising an antigen recognizing receptor that binds PSCA or CD19 with low affinity, wherein the binding activates the immunoresponsive cell, and a chimeric co-stimulating receptor (CCR) that binds PSMA and stimulates the immunoresponsive cell for use in the treatment of prostate cancer.

A kit comprising an immunoresponsive cell comprising an antigen recognizing receptor that binds a first antigen and activates the immunoresponsive cell, and a chimeric co-stimulating receptor (OCR) that binds a second viral antigen and stimulates the immunoresponsive cell.