Abstract: The present disclosure provides orthogonal chimeric cytokine receptor/orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

Abstract: Neurotoxicity associated with CD19-targeted CAR-T therapy is reduced by including an inhibitory CAR (iCAR) in the CAR-T cell, wherein the iCAR specifically recognizes an antigen specific for or associated with neurovascular mural cells (e.g. pericytes or vSMC).