Compositions and Methods for Treating Cancer with DuoCARs

An immunotherapy composition comprising:

• at least one multi-cistronic vector comprising a promoter operably linked to a multi-cistronic nucleic acid sequence encoding;
• two or more functional CARs comprising an extracellular antigen binding domain, a transmembrane domain, one or more non-identical intracellular signaling motifs, wherein each of the encoded two or more functional CARs comprises a non-identical amino acid sequence that is independently selected from the group consisting of the amino acid sequence of SEQ ID NOs. 54, 56, 60, and 62;
• and wherein the at least one multi-cistronic vector is used to genetically modify one or more lymphocyte populations.

(canceled)

(canceled)

-22. (canceled)

A pharmaceutical composition comprising an antitumor effective amount of a population of human lymphocyte cells, wherein each cell of the population of human lymphocyte cells comprises (a) at least one multi-cistronic vector;

• (b) wherein each of the at least one multi-cistronic vector encodes two or more functional CARs comprising a non-identical amino acid sequence that is independently selected from the group consisting of the amino acid sequence of SEQ ID NO. 54, 56, 60, and 62;
• (c) wherein each of the two or more functional CARs comprises an extracellular antigen binding domain, a transmembrane domain, at least one linker domain, and one or more non-identical intracellular signaling motifs;
• and (d) wherein the extracellular antigen binding domain, the transmembrane domain, the at least one linker domain, and the one or more intracellular signaling motifs are covalently linked in each of the at least one multi-cistronic vector, wherein the at least one multi-cistronic vector is used to genetically modify one or more lymphocyte populations.

-25. (canceled)

-38. (canceled)