Abstract: Provided herein are safe harbor loci that can be utilized as sites for genetic modification. Safe harbor loci of the disclosure are shown to support sustained transgene expression with minimal silencing, and minimal impact on local or global gene expression. Safe harbor loci disclosed herein can be used in various genetic and cell engineering applications.

Abstract: The present disclosure describes systems and methods for immunotherapies Immune cells can be engineered to exhibit enhanced half-life as compared to control cell (e.g., a non-engineered immune cell). Immune cells can be engineered to exhibit enhanced proliferation as compared to a control cell. Immune cells can be engineered to effectively and specifically target diseased cells (e.g., cancer cells) that a control cell otherwise is insufficient or unable to target. The engineered Immune cells disclosed herein can be engineered ex vivo, in vitro, and in some cases, in vivo. The engineered Immune cells that are prepared ex vivo or in vitro can be administered to a subject in need thereof to treat a disease (e.g., myeloma or solid tumors). The engineered Immune cells can be autologous to the subject. Alternatively, the engineered immune cells can be allogeneic to the subject.