Provided are methods of continuous counterflow centrifugation for the manufacturing of cell compositions, including for the production of T cell therapies including cells that express recombinant receptors such as chimeric antigen receptors (CARs).

The present disclosure describes a chimeric antigen receptors (CAR) that allow a cell of the B cell lineage to undergo antigen-induced activation independent of a cell of T cell lineage, compositions thereof, and method of use thereof for genetically modifying a cell of the B cell lineage or treating a subject suffering from a pathological disorder.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

Described herein are methods and compositions for treating a disease, e.g. cancer (including solid tumors) inflammatory disease, autoimmune disease, or fibrosis. Method for treating a disease in a subject, the method including administering to the subject a composition containing an oncolytic virus and an immune cell, wherein the immune cell is infected with an oncolytic virus.

The disclosure provides synthetic immune receptors (SIRs), nucleic acids encoding the SIRs, methods of making and using the SIRs, in, for example, adoptive cell therapy.

The present invention relates to compositions and methods for treating of a HIV infected mammal using a CD4 membrane-bound chimeric receptor or a HIV specific scFvs CARs. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with HIV infection.

The invention relates to novel chimeric antigen (CAR) mRNA molecules, the methods of generating the molecules and methods of treating cancer with the molecules.

The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.

Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Provided herein are compositions and methods for increasing transduction efficiency of cells (e.g., immune cells) with a viral vector by incubating said cells with one or more agents (e.g., AKT inhibitors and stains such as rosuvastatin) that increase transduction efficiency of cells.