Methods and compositions for transducing lymphocytes and regulating the activity thereof

A replication incompetent recombinant retroviral particle, comprising:

• A. one or more envelope polypeptides;
• B. 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 comprising a lymphoproliferative element wherein the lymphoproliferative element comprises a cytokine receptor polypeptide comprising a signaling domain that is capable of activating a Jak pathway, and promoting proliferation and/or survival of T cells;
• and
• ii. a second engineered signaling polypeptide comprising an antigen specific targeting region (ASTR), a transmembrane domain, and an intracellular activating domain;
• and
• C. an activation element on the surface of the replication incompetent recombinant retroviral particle, wherein the activation element is fused to a heterologous membrane attachment sequence, and wherein the activation element comprises a means for binding to CD3.