Enhancing activity of CAR T cells by co-introducing a bispecific antibody
AssigneeThe Trustees of the University of Pennsylvania
InventorsCarl H. June, Yangbing Zhao, Xiaojun Liu
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Abstract
The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a T cell, genetically modified to express a chimeric antigen receptor (CAR), a bispecific antibody, or a combination thereof to a subject. The CAR and bispecific antibody of the invention can comprise a human antibody, a humanized antibody, or antigen-binding fragments thereof.
Claims12
A method for stimulating a T cell-mediated immune response to a tumor cell population or tumor tissue in a mammal, the method comprising administering to the mammal an effective amount of a T cell, wherein the T cell is genetically modified to coexpress a CAR and a bispecific antibody, wherein the CAR comprises a tumor antigen binding domain, a transmembrane domain, and a CD3 zeta signaling domain, further wherein the tumor antigen binding domain is selected from the group consisting of a human antibody, a humanized antibody, and an antigen binding fragment thereof, thereby stimulating a T cell-mediated immune response to the tumor cell population or tumor tissue in the mammal, and wherein the bispecific antibody comprises a domain that binds a T cell antigen and does not comprise a transmembrane domain.
A method for stimulating a T cell-mediated immune response to a target tumor cell population or tumor tissue in a human, the method comprising administering to the human an effective amount of a T cell, wherein the T cell is genetically modified to express a CAR, and wherein the CAR comprises a polypeptide encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 20, SEQ ID NO:
- 21, and SEQ ID NO:
- 22, thereby stimulating a T cell-mediated immune response to the target tumor cell population or tumor tissue in the human.
A method of treating a mammal with a tumor or cancer associated with an elevated expression of a tumor antigen, the method comprising administering to the mammal an effective amount of a T cell, wherein the T cell is genetically modified to coexpress a CAR and a bispecific antibody, wherein the CAR comprises a tumor antigen binding domain, a transmembrane domain, and a CD3 zeta signaling domain, further wherein the tumor antigen binding domain is selected from a human antibody, a humanized antibody, and an antigen binding fragment thereof, thereby treating the mammal, and wherein the bispecific antibody comprises a domain that binds a T cell antigen and does not comprise a transmembrane domain.
A method of treating a human with a tumor or cancer associated with an elevated expression of a tumor antigen, the method comprising administering to the human an effective amount of a T cell, wherein the T cell is genetically modified to express a CAR, and wherein the CAR comprises a polypeptide encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 20, SEQ ID NO:
- 21, and SEQ ID NO:
- 22, thereby treating the human.
A method of treating a human with cancer, the method comprising administering to the human a T cell, wherein the T cell is genetically engineered to coexpress a CAR and a bispecific antibody, wherein the CAR comprises a tumor antigen binding domain, a transmembrane domain, and a CD3 zeta signaling domain, further wherein the tumor antigen binding domain is selected from a human antibody, a humanized antibody, and an antigen binding fragment thereof, and wherein the bispecific antibody comprises a domain that binds a T cell antigen and does not comprise a transmembrane domain.
A method of treating a human with cancer, the method comprising administering to the human a T cell, wherein the T cell is genetically engineered to express a CAR, and wherein the CAR comprises a polypeptide encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 20, SEQ ID NO:
- 21, and SEQ ID NO:
- 22.
Dependencies are inferred from the claim text.