Compositions and methods for treating cancer with DuoCARs
AssigneeLentigen Technology, Inc.
InventorsRimas Orentas, Dina Schneider, Waleed M. Haso, Stefan Miltenyi, Boro Dropulic
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Abstract
Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.
Claims8
A method of treating a subject having a CD19+, a CD20+, a CD22+ or a CD19+ and CD20+ lymphoma, the method comprising administering to the subject having the CD19+, the CD20+, the CD22+ or the CD19+ and CD20+ lymphoma a pharmaceutical composition comprising an antitumor effective amount of a population of human T cells,
- wherein the population of human T-cells are autologous to the subject, and wherein each cell of the population of human T-cells comprises at least one multi-cistronic vector, each of the at least one multi-cistronic vector comprises a promoter operably linked to a multi-cistronic nucleic acid sequence encoding two or more functional CARs, wherein at least one of the two or more functional CARs comprises two non-identical extracellular antigen binding domains, a transmembrane domain, and one or more non-identical intracellular signaling motifs,
- and comprises an amino acid sequence selected from the group consisting of SEQ ID NO:
- 10 and SEQ ID NO:
- 52, and
- the combination of the vectors results in the expression of at least two non-identical extracellular binding domains directed to the CD19+, the CD20+, the CD22+ or the CD19+ and CD20+ lymphoma thereby treating the subject.
A method of treating a subject having a lymphoma, the method comprising administering to the subject having the lymphoma a pharmaceutical composition comprising an antitumor effective amount of a population of human T-cells autologous to the subject,
- wherein each cell of the population of human T-cells autologous to the subject comprises at least one multi-cistronic vector, wherein the at least one multi-cistronic vector comprises a promoter operably linked to a multi-cistronic nucleic acid sequence encoding two or more functional CARs, wherein at least one of the two or more functional CARs comprises two non-identical extracellular antigen binding domains, a transmembrane domain, and one or more non-identical intracellular signaling motifs,
- and comprises non-identical amino acid sequences that are independently selected from the group consisting of the amino acid sequences of SEQ ID NO:
- 4;
- SEQ ID NO:
- 10;
- SEQ ID NO:
- 22;
- SEQ ID NO:
- 24;
- SEQ ID NO:
- 26;
- SEQ ID NO:
- 30;
- SEQ ID NO:
- 32;
- SEQ ID NO:
- 34;
- SEQ ID NO:
- 36;
- SEQ ID NO:
- 44;
- SEQ ID NO:
- 48;
- SEQ ID NO:
- 50;
- and SEQ ID NO:
- 52, and the combination of the vectors results in the expression of at least two non-identical extracellular binding domains, thereby treating the lymphoma in the subject.
Dependencies are inferred from the claim text.