Abstract: The present disclosure relates generally to compositions and methods useful for the production of engineered antibodies having (i) multiple antigen-binding specificities and (ii) Fc regions that have been modified to promote heterodimer formation between heavy chains from antibodies with different specificities. Also provided are recombinant cells, recombinant nucleic acids encoding such engineered antibodies, as well as pharmaceutical compositions containing same.

Abstract: Provided herein are CD70-binding proteins comprising a CD70-binding domain and a transmembrane domain, engineered immune cells comprising the CD70-binding proteins, and methods of making and using the same. Also provided herein are engineered immune cells e.g. CAR (chimeric antigen receptor) T cells for administration to patients to treat cancer (e.g., solid tumors and hematologic tumors) and other unwanted conditions. The cells are engineered to functionally express a first antigen binding molecule e.g. a CD70 CAR and a second antigen binding molecule e.g. a second CAR that binds a target molecule characteristic of the cancer or other disease or unwanted condition. The cells may be further engineered to reduce the functional expression level of one or more of TRAC, CD52 and CD70. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering them.

Abstract: A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

Abstract: Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-? ligand or a TGF-? receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and/or through engagement of a TGF-? ligand or a TGF-? receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.