Provided are T cell receptors (TCR) and TCR variable regions that can selectively bind a Hormad1 peptide/MHC complex. The TCR may be utilized in various therapies, such as autologous Hormad1-TCR adoptive T cell therapy to treat a cancer, such as a solid tumor expressing Hormad1. Methods for expanding related populations of T cells are provided.

Embodiments of the disclosure provide methods and compositions that facilitate cancer treatment including at least because they concern therapies that circumvent the tumor microenvironment. In specific embodiments, compositions are utilized for therapy that utilize tumor-infiltrating lymphocytes and/or engineered T cells that are protected from immunosuppression from the tumor microenvironment because they are engineered to have reduced or eliminated expression of transforming growth factor-beta receptor 2 and/or I-cell-Ig-and-ITIM-domain and/or CD7 genes.

Methods for generating/expanding populations of immune cells comprising immune cells specific for an Epstein Barr Virus (EBV) lytic antigen are disclosed, the methods comprising stimulating immune cells specific for an EBV lytic antigen by contacting peripheral blood mononuclear cells (PBMCs) with: (i) one or more peptides corresponding to all or part of one or more EBV lytic antigens; or (ii) antigen presenting cells (APCs) presenting one or more peptides corresponding to all or part of one or more EBV lytic antigens. Also disclosed are populations of immune cells comprising immune cells specific for an EBV lytic antigen expanded according to such methods, and uses thereof.

The present invention is directed to the field of immunotherapy. Specifically, the invention provides compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the invention are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

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.

The present invention concerns a biomarker useful in adoptive cell therapy. The biomarker in question is CD150, otherwise termed SLAM or SLAMF1. Herein Applicants demonstrate that expression of CD150 on tumour infiltrating lymphocytes infusion products correlates with the response rate seen in those patients. High CD150 expression is found on patients who go on to have a complete response and low expression on patients who do not respond to therapy. The invention relates to the use of the biomarker to predict response rate or stratify patients for treatment. It also covers exploitation of this receptor in adoptive cell therapy regimens in general, including but not limited to over expression of the receptor in T-cell populations or isolation of cells expressing CD150 in an effort to increase efficacy.

Provided are compositions including EGFR mutant peptides that bind to HLA class I and/or HLA class II complexes and compositions comprising a plurality of such peptides. Methods for treating EGFR-mutant cancers with peptides of the embodiments are likewise provided. Methods for expanding related populations of immune effector cells, such as T cells, are also provided.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the used thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The present invention relates to an immune cell, which contains a TMEM59 protein and/or a functional fragment thereof, a chimeric antigen receptor (CAR) and/or a coding element thereof, as well as a use of the immune cell in the preparation of a drug for treating tumors. Further provided are a method for promoting the proliferation of immune cells and a method for promoting the production of memory cells.

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions including apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do not reduce the efficacy of the CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm including administration of a composition including apoptotic cells or an apoptotic cell supernatant.