An in vitro method of expanding T cells includes isolating T cells from a blood sample of a human subject, activating the isolated T cells in the presence of an aminobisphosphonate and/or a feeder cell and at least one cytokine, expanding the activated T cells, and optionally restimulating the expanded T cells.

This invention relates to modified T cells that inducibly express a bioactive molecule, such as IL-7, and constitutively expresses an antigen receptor, such as a T cell receptor or chimeric antigen receptor that binds to a tumour antigen. The modified T cells may comprise a nucleic acid construct that comprises a first nucleotide sequence encoding the bioactive molecule, a second nucleotide sequence encoding the antigen receptor; an inducible promoter operably linked to the first nucleotide sequence and a constitutive promoter operably linked to the second nucleotide. Nucleic acid constructs and vectors are provided, as well as T cells comprising such constructs and vectors and therapeutic methods and uses thereof.

The technology relates in part to methods for controlling the activity or elimination of therapeutic cells using molecular switches that employ distinct heterodimerizer ligands, in conjunction with other multimeric ligands. The technology may be used, for example to activate or eliminate cells used to promote engraftment, to treat diseases or condition, or to control or modulate the activity of therapeutic cells that express chimeric antigen receptors or recombinant T cell receptors.

The present disclosure relates to T cells capable of co-expressing T cell receptors (TCR) together with CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods thereof.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

The present disclosure relates to T cells capable of co-expressing T cell receptors (TCR) together with CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods thereof.

Combinations comprising one or more nucleic acid molecules comprising a nucleic acid sequence A encoding for a TCR alpha chain linked to a dimerization domain, and a nucleic acid sequence B encoding for a TCR beta chain linked to a dimerization domain, as well as proteins encoded by such nucleic acid molecules and corresponding uses and methods.

The present disclosure provides methods for treating a progressive ovarian cancer using an allogeneic leukemia-derived cell. Also provided are immunogenic compositions comprising an allogeneic leukemia-derived cell, and pharmaceutical compositions and formulations thereof.

Disclosed are nucleic acid constructs comprising a promoter; a nucleic acid sequence encoding a single-chain variable fragment (scFv); a nucleic acid sequence encoding a notch transmembrane domain; and a nucleic acid sequence encoding a transcription factor. Disclosed are vectors comprising any of the disclosed nucleic acid constructs. Disclosed are proteins comprising a scFv; a notch transmembrane domain; and a transcription activator. Disclosed are methods of increasing human leukocyte antigen class I (HLA-I) on the surface of a tumor cell in a subject comprising administering to the subject one or more of the recombinant cells or compositions comprising a recombinant cell disclosed herein.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.