The invention relates to methods for the isolation of non-haematopoietic tissue-resident lymphocytes, particularly γδ T cells. Such γδ T cells include non-Vδ2 cells, e.g. Vδ1, Vδ3 and Vδ5 cells and such non-haematopoietic tissues include skin and gut. It will be appreciated that such isolated non-haematopoietic tissue-resident lymphocytes find great utility in adoptive T cell therapies, chimeric receptor therapies and the like. Also provided are methods for expanding isolated tissue-resident lymphocytes, particularly methods for isolating and expanding γδ T cells. The present invention also relates to both individual cells and populations of cells produced by the methods described herein.

A seed cell medium of a tumor-infiltrating lymphocyte and an application thereof. The medium contains a cell culture component, a cell factor, and an immune checkpoint antibody or an antigen-binding fragment thereof. The cell factor includes IL-2; an immune checkpoint includes PD-1, LAG-3, TIGIT, and/or CTLA-4; and the cell culture component is a serum medium or a serum-free medium. The seed cell medium accelerates a culture of a seed cell of the tumor-infiltrating lymphocyte and shortens the amplification time required by the tumor-infiltrating lymphocyte.

Provided herein are tumor-antigen VGLL 1 specific T cell receptors. The TCR may be utilized in various therapies, such as autologous cell transplantation, to treat a cancer. Methods for expanding a population of T cells that target VGLL 1 are also provided.

Embodiments of the disclosure includes methods of producing viral-specific therapy (VST) cells specific for the SARS-CoV-2 virus and uses of the cells. The methods may utilized peptide mixtures and stimulation of mononuclear cells using particular cytokine cocktails. The cells may also be genetically modified to lack expression of one or more endogenous genes, including one or more genes that renders the cells more effective and/or able to withstand deleterious conditions, such as the presence of glucocorticoids.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, the expansion employing a feeder cell population.

Embodiments of the disclosure encompass methods and compositions for producing engineered B cells. The disclosure concerns large-scale processes for producing B cells that are engineered to have disruption of expression of one or more genes using CRISPR and also express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process.

Embodiments of the disclosure encompass methods and compositions for producing engineered T cells. The disclosure concerns large-scale processes for producing T cells that may be engineered to have disruption of expression of one or more genes using CRISPR and also express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process. The T cells may or may not be viral-specific.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. The methods may comprise gene-editing at least a portion of the TILs to enhance their therapeutic efficacy. Such TILs find use in therapeutic treatment regimens.

Provided is a non-naturally occurring T population, of which the proportion of T memory stem cells satisfies C1≥50%. The T cell population comprises a tumor antigen-targeting universal CAR-T cell. Further provided is a method for preparing the CAR-T cell. The CAR-T cell is higher in amplification rate and better in phenotype, IFN-gamma releasing capacity and target cell killing capability.

The invention relates to: a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising an IL-2 protein and a CD80 protein; and a method for preparing natural killer cells by using same. Particularly, a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising IL-2 or a variant thereof and CD80 or a fragment thereof, of the present invention; promotes the proliferation of natural killer cells, induces the expression of CD16 and NKp46, and increases the expression and secretion of granzyme B and perforin, thereby being effectively usable in the preparation of natural killer cells having an excellent anticancer immune function.