The present invention relates to an engineered immune cell endowed with a new CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect said immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Provided herein are genetically modified ungulate cells expressing a chimeric antigen receptor. Also provided herein are transgenic ungulate cells that can be used as cell carriers for the delivery of oncolytic viruses in cancer therapy. Also provided are transgenic ungulates comprising these cells, methods of making these cells, and methods of treating cancer by administering these cells to a subject in need thereof. Also provided are transgenic ungulate cells that express a chimeric antigen receptor and uses thereof.

The present invention provides a chimeric antigen receptor (CAR) comprising a CD21-binding domain, a transmembrane domain and an intracellular domain.

An aptamer-based switch technology is provided that enhances control of the use of chimeric antigen receptor (CAR)-related immunotherapies. The aptamer-based switch utilizes a synthetic bridge molecule containing a target-binding aptamer bound through a linker to a CAR-binding aptamer. A system containing a CAR and a corresponding aptameric bridge provides an immunotherapy platform that: (i) can be targeted to any desired antigen by choosing the target-binding aptamer of the bridge. (ii) can be redirected from one target to another by changing the target-binding aptamer: (iii) can be dosed according to the changing needs of an individual patient overtime by altering the administration protocol for the bridge: (iv) can be switched on or off quickly or gradually: (v) can be used as a companion diagnostic for a specific CAR therapy: (vi) can be integrated with either in vivo or ex vivo CAR expression: (vii) is non-immunogenic; and (viii) has low production costs.

The present invention relates to using monoterpene or sesquiterpene to permeabilize the blood brain barrier.

The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods are capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and/or resources and/or reduced handling compared with other methods.

The present disclosure relates to CAR-T cells and uses thereof. Disclosed herein is a genetically modified T cell comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) polypeptide comprising a single-chain variable fragment (scFV) that specifically binds to a target molecule, wherein the nucleic acid sequence encoding the CAR polypeptide is integrated into an integration site located at a miR-155 host gene.

Provided herein are methods and compositions for treating a subject having myasthenia gravis using T cells engineered with a chimeric antigen receptor that binds CD19. Also provided herein are methods and compositions for treating a subject having stiff person syndrome using T cells engineered with a chimeric antigen receptor that binds CD19.

Chemically induced dimerizers (AbCIDs) have emerged as one of the most powerful tools to artificially regulate signaling pathways in cells; however, no facile method to identify or design these systems currently exists. The present invention provides a methodology to rapidly generate antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule-protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. Success of this strategy is demonstrated by generating ten chemically-inducible antibodies against the BCL-xL/ABT-737 complex. Three of the antibodies are highly selective for the BCL-xL/ABT-737 complex over BCL-xL alone. Two exemplary important cellular applications of AbCIDs are demonstrated by applying them intracellularly to induce CRISPRa-mediated gene expression and extracellularly to regulate CAR T-cell activation with the small molecule, ABT-737. ABT-737 is not toxic at the concentrations used to activate AbCIDs in cells. AbCIDs provided by this invention are new and orthogonal AbCIDs, expanding the limited toolbox of available CIDs.

The present invention provides composition kits and methods for treating cancer in a human by immunotherapy using successive doses of CAR-T cells with no or reduced anamnestic immune reaction in one individual (P).