Methods of culturing T cells with a 4-1BBL fusion polypeptide are provided. Accordingly there is provided a method of culturing T cells comprising adding to immune cells comprising T cells obtained from a subject having a pathology a PD1-4-1BBL or a SIRPalpha-4-1BBL fusion polypeptide; and culturing the immune cells with the fusion polypeptide for more than 7 days. Also provided are T cells obtainable by the method and uses thereof.

Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

Methods of culturing embryonic stem cells, induced pluripotent stem cells and/or differentiated cells in culture medium comprising activin are described. In one aspect, the disclosure features a pluripotent human stem cell, wherein the stem cell comprises: (i) a genomic edit that results in loss of function of Cytokine Inducible SH2 Containing Protein (CISH) and (ii) a genomic edit that results in a loss of function of an agonist of the TGF beta signaling pathway, or a genomic edit that results in a loss of function of adenosine Ata receptor.

Methods of culturing embryonic stem cells, induced pluripotent stem cells and/or differentiated cells in culture medium comprising activin are described. In one aspect, the disclosure features a pluripotent human stem cell, wherein the stem cell comprises: (i) a genomic edit that results in loss of function of Cytokine Inducible SH2 Containing Protein (CISH) and (ii) a genomic edit that results in a loss of function of an agonist of the TGF beta signaling pathway, or a genomic edit that results in a loss of function of adenosine Ata receptor.

A method for predicting the cell spatial relation based on single-cell transcriptome sequencing data includes the steps of obtaining a probability matrix P of a cell-cell interaction strength matrix A based on single-cell transcriptome sequencing data; reconstructing, according to the obtained probability matrix P of the cell-cell interaction strength matrix A, a three-dimensional spatial structure in which cells interact with each other; and for each cell in the reconstructed three-dimensional spatial structure in which cells interact with each other, determining the intercellular distance threshold for each cell to interact with h cells on average to obtain an intercellular interaction network. The method requires only the single-cell transcriptome sequencing data to predict the interaction of the cells in three-dimensional space, which breaks the limitation of the existing technology that needs to obtain the spatial relationship of cells through imaging.

This disclosure describes genetically engineered natural killer (NK) cells, pharmaceutical compositions that include these NK cells, and methods of making and using these NK cells.

This disclosure describes genetically engineered natural killer (NK) cells, pharmaceutical compositions that include these NK cells, and methods of making and using these NK cells.

The present disclosure provides compositions and methods for cell transplantation therapy based on forced expression of an exogenous HLA-F protein in donor cells to be transplanted into a subject. In some embodiments, the donor cells express an exogenous chimeric HLA-F protein comprising an extracellular region comprising an HLA-F alpha 1 domain, an HLA alpha 2 domain, an HLA-F alpha 3 domain, a linker and a β2m protein.

The present disclosure provides compositions and methods for cell transplantation therapy based on forced expression of an exogenous HLA-F protein in donor cells to be transplanted into a subject. In some embodiments, the donor cells express an exogenous chimeric HLA-F protein comprising an extracellular region comprising an HLA-F alpha 1 domain, an HLA alpha 2 domain, an HLA-F alpha 3 domain, a linker and a β2m protein.