Methods and compositions for genetically modifying lymphocytes to express polypeptides comprising the intracellular domain of CD79A and CD79B

A vector, comprising:

• a polynucleotide comprising one or more transcriptional units, wherein each of the one or more transcriptional units is operatively linked to a promoter active in T cells, and wherein the one or more transcriptional units encode:
• i. a first engineered signaling polypeptide, wherein said first engineered signaling polypeptide is a chimeric polypeptide comprising an extracellular domain, a transmembrane domain, and a first intracellular signaling domain capable of activating a cellular signaling pathway, wherein said transmembrane domain is covalently attached to said extracellular domain and said first intracellular signaling domain,
• wherein said transmembrane domain is between 15 and 100 amino acids,
• wherein said first intracellular signaling domain comprises an intracellular signaling domain that comprises a first ITAM motif, wherein the first ITAM motif comprises the sequence YX1X2L/I, wherein X1 is any amino acid and X2 is any amino acid,
• wherein said first intracellular signaling domain is selected from CD79A having at least 90% sequence identity to the sequence of SEQ ID NO:210 and CD79B having at least 90% sequence identity to the sequence of SEQ ID NO:211, and
• wherein said extracellular domain comprises a leucine zipper dimerizing motif, and
• ii. a second engineered signaling polypeptide comprising a chimeric antigen receptor (CAR) or a recombinant TCR.