This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

Control Devices are disclosed including RNA destabilizing elements (RDE), and RNA control devices, combined with transgenes, including Chimeric Antigen Receptors (CARs) in eukaryotic cells. RDEs can be combined with RNA control devices to make RDEs that include ligand mediated control. These smart RDEs and other RDEs can be used to optimize expression of transgenes, e.g., CARs, in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered at desired times from the eukaryotic cell.

Embodiments herein relate to humanized CD19 antibodies and disease treatment using the antibodies. For example, a subject having a CD19 positive tumor may be administered a therapeutically effective amount of the humanized antibody.

Provided are a fusion protein comprising an antibody binding area and an endocytic functional area, the encoding nucleic acid of the protein, an expression vector of same, a host cell thereof, and an immune effector cell expressing the fusion protein or the endocytic functional area or further expressing a chimeric antigen receptors. Also provided are an immunoconjugate comprising a cell-killing part and an antibody conjugate in a specifically-binding immune effector cell or an antibody of the endocytic functional area, a reagent kit and uses of the immunoconjugate, and a method for specifically removing, selecting, or enriching and detecting the immune effector cell.

Provided herein are methods of modulating, in vivo, cells engineered with a recombinant receptor, such as a T cell receptor (TCR) or chimeric antigen receptor (CAR). In some embodiments, the methods include disrupting an area in the subject in which the cells are present or likely to be present or were present or were likely to be present, such as a lesion, including a tumor. In some embodiments, the disruption alters the environment of the lesion, e.g. tumor microenvironment. In some embodiments, the disruption is a biopsy. In some aspects, the provided methods result in increased expansion, and, in some cases, a more robust and durable response, of the engineered cells after carrying out the disruption.

Described herein are compositions including an immune effector cells that are chemically modified at the surface with one or more active agent-loaded nano- or micro-particles for controlled release of the active agent. Exemplary drug-loaded nanoparticles include crosslinked multilayer liposome (CMLV) encapsulating an A2a receptor inhibitor. The modified immune effector cells may also present one or more chimeric antigen receptors (CARs) on the surface. Also provided are methods of using the same to treat cancer.

Control Devices are disclosed including RNA destabilizing elements (RDE), and RNA control devices, combined with transgenes, including Chimeric Antigen Receptors (CARs) in eukaryotic cells. RDEs can be combined with RNA control devices to make RDEs that include ligand mediated control. These smart RDEs and other RDEs can be used to optimize expression of transgenes, e.g., CARs, in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered at desired times from the eukaryotic cell.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

The present invention relates to immune cell-based anti-cancer therapeutics and methods of using the therapeutics in the treatment of cancer.

Disclosed herein include methods of inducing expansion of modified effector cells in vivo which comprise administration of a steroid and modified effector cells. Also described herein include methods of inducing expansion of modified T cells (e.g., CAR-T cells or TCR cells) in vivo, which comprise administration of a steroid and modified T cells.