Methods of expanding tumor infiltrating lymphocytes (TILs) from cryopreserved tumor tissue and methods of using the expanded TILs in the treatment of human diseases, including cancers, are disclosed. Preparing the tumor tissue for freezing includes fragmenting the tumor tissue, and incubating the fragments in a cryopreservation medium. In an embodiment, the fragments may be incubated in the cryo preservation medium at 2° C. to 8° C. for about 30 to about 80 minutes. Freezing the fragments may be done by flash freezing using the vapor phase of liquid nitrogen, e.g. using a dry cryoshipper. In some embodiments, compositions of cryopreserved tumor tissues are disclosed.

Cartridges for manufacturing a population of cells suitable for formulation as a cellular therapeutic are disclosed herein, along with systems and instruments for operating the cartridges and performing methods to generate the population of cells suitable for formulation as a cellular therapeutic. The population of cells suitable for formulation as a cellular therapeutic can be immunological cells, such as T lymphocytes, including endogenous T cells (ETCs), tumor infiltrating lymphocytes (TILs), CAR T-cells, TCR engineered T-cells, or otherwise engineered T-cells. The systems and methods can be largely automated.

The present invention provides methods of expanding γδ T cells from a non-haematopoietic tissue source. Further provided are compositions of expanded γδ T cells and methods of using the expanded γδ T cells (e.g., apart of an adoptive T cell therapy).

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.

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 specific to mesothelin and a second inhibitory receptor specific to a ligand that has been lost in a mesothelin-positive cancer cell, and methods of making and using same for the treatment of cancer.

The present disclosure provides a method for treating a subject having a coronavirus infection comprising administering to the subject at least one dose of a population of natural killer (NK) cells in an amount effective to reduce the coronavirus infection in the subject. In various embodiments, the NK cells administered to the subject are isolated NK cells, expanded and activated NK cells, or placental-derived NK cells.

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.

The application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described.

Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.