Abstract: This disclosure relates to, inter alia, polynucleotides encoding modified interleukin 2 (IL-2) polypeptides and fusion proteins comprising such modified IL-2 polypeptides, vectors comprising such polynucleotides, pharmaceutical compositions comprising such polynucleotides and vectors, and methods of treating diseases and disorders by administering such polynucleotides, vectors, and/or pharmaceutical compositions.

Abstract: The present disclosure provides engineered chimeric T cell receptors and subunit polypeptides that include a single chain antibody (ScFv) that binds a target antigen fused to at least a portion of a constant region of a TCR? chain or at least a portion of a constant region of a TCR? chain. Also provided are nucleic acid molecules that encode the engineered T cell receptors and subunit polypeptides, transgenic cells expressing the engineered T cell receptors and polypeptides, and methods of using the transgenic cells for the treatment of cancer.

Abstract: The present disclosure provides transgenic cells that express memory dimeric antigen receptors (mDARs), where the mDAR constructs comprise a JAK-STAT intracellular region having a cytokine receptor intracellular region which includes Box 1 and Box 2 motifs for binding a Janus kinase (JAK) which can play a role in JAK-STAT cellular signaling pathway to induce effector cell activation and proliferation. In one embodiment, the JAK-STAT intracellular region further comprises a CD3zeta intracellular signaling region having an intact ITAM region, or having ITAM 1 and 3, or having only ITAM 3 with a partial deletion. Transgenic cells expressing the mDAR constructs exhibit potent cytotoxicity, and release reduced levels of cytokines, compared to traditional DARs that lack a cytokine receptor intracellular region. The mDAR constructs have antibody-like properties as they bind specifically to a target antigen. Transgenic cells expressing the mDAR constructs can be used for directed cell therapy.