abstract |
The present disclosure provides methods for genetically modifying lymphocytes, comprising transducing T cells and/or NK cells without prior ex vivo stimulation, and methods for performing adoptive cell therapy. The methods typically involve engineered signaling polypeptides that may include a lymphocyte proliferative element, and/or a chimeric antigen receptor (CAR), eg, a microenvironment restricted CAR. Provided herein are additional elements of the engineered signaling polypeptides, as well as vectors such as retroviral vectors, packaging cell lines and methods of making them. Further provided are recombinant retroviruses and methods of making the same. A number of control devices are provided, including, for example, riboswitches controlled by nucleoside analogs in vivo. |