Disclosed herein are anti-BCMA antibodies and antigen-binding fragments, chimeric antigen receptors (“CARs”) having these anti-BCMA antibodies and antigen-binding fragments (“BCMA CARs”) and genetically modified immune effector cells having such BCMA CARs. Polynucleotides encoding the anti-BCMA antibodies and antigen-binding fragments and BCMA CARs are also provided herein. Compositions comprising anti-BCMA antibodies and antigen-binding fragments and BCMA CARs are also provided herein. The present disclosure also relates to use of the anti-BCMA antibodies and antigen-binding fragments and genetically modified immune effector cells having such BCMA CARs in cancer treatment.

The present disclosure provides feeder hydrogel particles that can function to support the growth, proliferation, and/or activation of a target cell in culture. The present disclosure also provides methods of culturing target cells with feeder hydrogel particles.

Provided herein are methods that relate, in some aspects, to the incubation or culturing, such as to induce stimulation of expansion (proliferation), activation, costimulation and/or survival, of a composition of cells, such as a population of lymphocytes. In some aspects, provided are methods and reagents for the stimulation, e.g., of expansion (proliferation), survival or persistence, activation, costimulation, or other effect, of cell populations that involve binding of agents to a molecule on the surface of the cells, thereby providing one or more signals to the cells. In some cases, the reagents are reagents containing a plurality of binding sites for agents, such as multimerization reagents, and thus the one or more agents are multimerized by reversibly binding to the reagent, e.g., thereby creating a stimulatory reagent (multimerized agent), having stimulatory agents multimerized thereon. In some aspects, the multimerized agent can provide for expansion or proliferation or other stimulation of a population of cells, and then such stimulatory agents can be removed by disruption of the reversible bond. Also provided are compositions, apparatus and methods of use thereof.

The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.

The disclosure provides immune cells comprising a first activator receptor and a second inhibitory receptor, and methods of making and using same for the treatment of cancer.

The invention is directed to a process for providing a cell comprising a chimeric antigen receptor (CAR) specific for one or more target antigens exposed on tumor microenvironment cells characterized by providing a cell sample comprising tumor microenvironment cells and non-tumor microenvironment cells and repeating the steps of—contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety—removing unbound conjugate from the cell tissue and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates—erasing the fluorescence emitted by the fluorescent moieties of the conjugates until identifying at least two conjugates provided with antigen recognizing moieties recognizing different antigens, allowing in combination to discriminate between tumor microenvironment cells and non-tumor microenvironment cells and providing cells with the identified at least two antigen recognizing moieties as chimeric antigen receptor (CAR). Preferable, the tumor microenvironment cells are tumor microenvironment cells from tumor stromal cells or PaCa cells.

The present disclosure provides chimeric antigen receptors (CARs), and nucleic acids comprising nucleotide sequences encoding the CARs, that bind to HER2, and conditionally active biologic (CAB) CARs that bind to HER2. The present disclosure provides cells genetically modified to produce the CARs, delivery suspensions comprising these genetically modified cells, and methods for making such cells. The CARs of the present disclosure can be used in various methods, which are also provided, including methods for activating immune cells under certain conditions, and methods for performing adoptive cell therapy such as CAR therapy, for example CAR therapy against cancer.

In some embodiments, methods of delivering a therapeutically effective amount of an expanded number of tumor infiltrating lymphocytes obtained from tumor remnants to a patient in need thereof, for the treatment of a cancer, are disclosed.

In some embodiments, compositions and methods re¬lating to isolated artificial antigen presenting cells (aAPCs) are dis¬closed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors com¬prise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

Provided herein are methods for the activation and expansion of genetically-modified Tcells, such as tumor infiltrating lymphocytes. In some cases, cells of the embodiments can be used for the therapeutic treatment of human diseases, such as cancer.