The invention provides methods of treating CD-19 positive malignancies in human subjects with suitable doses of switchable CAR-T cells and complementary switch molecules.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.

Provided are compositions and methods for a cell population comprising engineered stem cells comprising a synthetic cytokine receptor for a non-physiological ligand. The non-physiological ligand activates the synthetic cytokine receptor in the engineered stem cells to induce differentiation of the stem cells and, expansion and/or activation of resulting cytotoxic innate lymphoid cells.

The present application relates to PD-1 switch receptors, e.g., chimeric PD-1 switch receptors, in combination with a FAS dominant negative receptor, optionally in combination with a safety switch, e.g., truncated EGFR, which can be used in adoptive cell therapy to treat human diseases and disorders.

Embodiments of the present disclosure relate generally to compositions and methods for the design of remote controlled biological systems, and more specifically to synthetic bioswitches that provide the ability to non-invasively and remotely control the function and activity of live cells, such as for example and not limitation, the expression of biologically active proteins or biological therapeutics, and the manipulation of physiologic or genetic processes and/or protein expression in live cells, in vivo (including, e.g., at desired anatomical sites) or ex vivo.

The present invention concerns a human T cell or NK cell comprising a nucleic acid construct which comprises a transgene which is placed under the control of a regulatory polynucleotide inducible by a deficiency in at least one essential amino acid. and cellular immunotherapy employing said human T cell or NK cell.

The invention relates to heterodimeric inactivatable chimeric antigen receptors (CARs) and their use for treatment.

Disclosed herein, in some aspects, are engineered avidity switch polypeptides, polynucleotides encoding the same, immune cells comprising the same, and compositions comprising the polypeptides, polynucleotides, and/or immune cells. In certain embodiments, engineered avidity switch polypeptides comprise one or more CD6 derived amino acid sequences and/or domains. In certain embodiments, engineered avidity switch polypeptides comprise engineered arrangements of extracellular domains of CD6 polypeptides. Also disclosed are methods for disease treatment, such as cancer treatment, comprising administering such immune cells and/or compositions to a subject in need thereof.

The present disclosure provides a versatile and multi-functional platform for transcriptome regulation using the RNA-guided. RNA-targeting activity of type VI-D CRISPR effectors with RNA-guided RNA endonuclease activity combined with guide arrays that express a plurality of guide RNAs. The system can be used to perform quantitative, reversible, and massively-multiplexed gene knockdown in primary human T cells and to perform multiplexed suppression of exhaustion-associated genes in T cells. The system can be used to enhance the anti-tumor activity of dysfunctional CAR T cells.