The present disclosure provides methods of preparing immune cells, e.g., T cells and/or NK cells, comprising contacting the cells with programmable cell-signaling scaffolds in a medium comprising at least about 5 mM potassium ion. In some aspects, the methods disclosed herein increase the number of less-differentiated cells in the population of cells. In some aspects, the cultured cells are engineered, e.g., to comprise a chimeric antigen receptor (CAR) or an engineered T cell receptor (TCR). In some aspects, the cells are administered to a subject in need thereof.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

Among the various aspects of the present disclosure is the provision of compositions and methods of making modified chimeric antigen receptor dendritic cells (CAR-DCs) and methods of use thereof. CAR-DCs can be used for the treatment of tumors and cancers, particularly solid tumors (as well as liquid tumors, blood cancer, and metastatic cancer).

The present invention relates to a method and system for identifying and validating pairs of candidate antigens and their cognate antigen-specific T lymphocytes that are useful for validating the immunogenic activity of paired antigen and TCR sequences. The method includes, inter alia, steps of determining one or more splice variants that are more highly transcribed in a sample obtained e from cohort of patients compared to a reference sample, determining one or more amino acid sequences that occur in an amino acid translation of said one or more splice variants but not in the corresponding splice variant in the reference sample, and predicting HLA binding of the amino acid sequences in order to identify candidate shared antigen. The present invention also relates to methods of characterising and/or treating a medical condition, including cancer.

The present disclosure describes systems and methods for immunotherapies Immune cells can be engineered to exhibit enhanced half-life as compared to control cell (e.g., a non-engineered immune cell). Immune cells can be engineered to exhibit enhanced proliferation as compared to a control cell. Immune cells can be engineered to effectively and specifically target diseased cells (e.g., cancer cells) that a control cell otherwise is insufficient or unable to target. The engineered Immune cells disclosed herein can be engineered ex vivo, in vitro, and in some cases, in vivo. The engineered Immune cells that are prepared ex vivo or in vitro can be administered to a subject in need thereof to treat a disease (e.g., myeloma or solid tumors). The engineered Immune cells can be autologous to the subject. Alternatively, the engineered immune cells can be allogeneic to the subject.

The present invention is intended to develop a chimeric antigen receptor (CAR) that is effective against solid tumor expressing anaplastic lymphoma kinase (ALK). The present invention provides a polynucleotide encoding a CAR protein comprising a target binding domain binding to an extracellular ligand binding region of ALK, a transmembrane domain, and an intracellular signaling domain. The target binding domain of the polynucleotide is selected from among FAM150A, FAM150B, and fragments thereof binding to the extracellular ligand binding region of ALK. The present invention also provides a genetically modified cell comprising the polynucleotide introduced thereinto.

Provided herein are methods of making a T cell comprising increasing a level of a AMPKγ2 polypeptide in the T cell wherein the T cell has the increased level of the AMPKγ2 polypeptide has an increased oxidative metabolism as compared to the control. The T cells made using these methods are included herein and can be used for increasing an immune response in a subject.

The preset disclosure provides chimeric activation receptors comprising (i) a TGFβ-binding domain and (ii) a CD2 costimulatory domain. In some aspects, the TGFβ-binding domain comprises an extracellular domain of a TGFβ receptor. Other aspects of the disclosure are directed to nucleic acid molecules encoding a chimeric activation receptor, cells comprising the chimeric activation receptor and/or a nucleic acid molecule encoding the same, and methods of use thereof in the treatment of a disease or condition (e.g., a tumor) in a subject in need thereof.

The present invention relates to tumor antigens encoded in a 5-upstream open reading frame (uORF) within the 5 UTR of different mRNAs. Compositions and peptides comprising such tumor antigens and a virus encoding such tumor antigens are provided. The present invention also relates to the use of such compositions, peptides and viruses in the treatment of cancer.

The present invention provides compositions and methods for inhibiting one or more diacylglycerol kinase (DGK) isoform in a cell in order to enhance the cytolytic activity of the cell. In one embodiment, the cells may be used in adoptive T cell transfer. For example, in some embodiments, the cell is modified to express a chimeric antigen receptor (CAR). Inhibition of DGK in T cells used in adoptive T cell transfer increases cytolytic activity of the T cells and thus may be used in the treatment of a variety of conditions, including cancer, infection, and immune disorders.