The present disclosure is directed towards genetically engineered TCR-T cells to recognize tumor antigens and simultaneously secrete a binding protein that blocks an immune checkpoint molecule and TGF. These engineered T cells demonstrate stronger antitumor response and reduced T cell exhaustion. The present disclosure provides immunotherapy against HPV- or EBV-positive cancers, among others.

Embodiments of the disclosure concern methods and compositions related to targeted cancer therapy directed to a particular terminal deoxynucleotidyl transferase peptide associated with HLA-A02. In specific embodiments, cellular therapy employs cells encoding a chimeric T-cell receptor that targets the peptide and optionally also a bi-specific T-cell engager that targets the same peptide. In particular embodiments, one or both are used to treat a hematological malignancy.

Dual-chimeric antigen receptor (CAR) cell systems are disclosed that can be used with adoptive cell transfer to target and kill cancers expressing tumor antigens (TA) that are also expressed on healthy hematopoietic cells. In some embodiments, the dual CAR cell expresses a first CAR polypeptide that contains in an ectodomain a binding agent that can selectively bind CD83 on CD83-expressing cancer cells (anti-CD83 binding agent), and a second CAR polypeptide that contains in an ectodomain an antigen-binding agent that can bind a second tumor antigen that is expressed on both the cancer and healthy hematopoietic cells (anti-TA binding agent), such as CD33, CLEC12A, CD123, or FLT3.

The present disclosure provides adoptive T cell therapies that have improved architectures for targeting antigens and recruiting multimeric immune signaling complexes for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Provided herein are FRAME immunogenic peptides, binding proteins recognizing FRAME immunogenic peptides, and uses thereof.

The disclosure is directed to methods and compositions for treating cancers characterized by cells comprising chimeric antigen receptors (CARs) that bind CD70 and T-cell engaging antibody molecules (TEAMs) that bind CD33, nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind CD70 and/or TEAMs that bind CD33, and compositions and methods related thereto.

The preset disclosure provides methods of culturing cells, e.g., pluripotent cells, multipotent cells, and/or immune cells (e.g., T cells, NK cells, and/or TILs) in a medium comprising at least about 5 mM potassium ion, wherein the medium is not hypertonic. In some aspects, the medium is hypotonic. In some aspects, the methods disclosed herein increases 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 or an engineered T cell receptor. In some aspects, the cells are administered to a subject in need thereof.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.

The present disclosure relates to immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. The present disclosure also relates to uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease.