A population of improved tumor infiltrating lymphocytes (TILs). These TILs have increased metabolic activity (MA), and increased therapeutic efficacy for cancer treatment, allowing applying reduced cell doses to a subject in need thereof. Further disclosed are methods for selecting a population of TILs with increased metabolic activity, methods for producing, and methods for using said TILs.

We provide new methods of in vitro or in vivo enhancing the T-cell stimulatory capacity of human DCs and the use thereof in cancer vaccination. The method includes the introduction of different molecular adjuvants to human DCs by contacting or modifying them with mRNA or DNA molecule(s) encoding CD40L, and CD70 or constitutively active TILR4 (caTLR4).

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.

The present invention provides a modified iPSC or haemogenic lineage cell, such as a T cell, comprising at least one heterologous nucleic acid sequence encoding a heterologous T-cell receptor (TCR) integrated in the cell genome, for example in the eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) gene and uses thereof.

Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. These cells are seen as drivers of tumor establishment and growth, often correlated to aggressive, heterogeneous and therapy-resistant tumors. Novel tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) specifically expressed by CSCs are described herein. Most of the TSAs described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells, antibodies and vaccines derived from these TSAs are described. The use of the TSAs, nucleic acids, compositions, antibodies, cells and vaccines for the treatment of cancer, and more particularly cancers associated with the presence of CSCs such as poorly differentiated cancers, is also described.

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 present invention provides a modified T cell or population of modified T cells comprising a heterologous recombinant T cell receptor (TCR) and heterologous recombinant co-receptor, additionally provided are methods of producing the modified T cell or population of modified T cells and their use in the treatment of cancer.

A peptide or composition comprising at least one HLA-A2 epitope or analog from CEA, HER2/neu, MAGE2, MAGE3, or p53.

The technology relates in part to methods for inducing partial apoptosis of cells that express an inducible caspase polypeptide. The technology further relates in part to methods for inducing partial apoptosis of cells that express an inducible modified caspase polypeptide, having a modified dose response curve to the multimeric ligand inducer. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide or the inducible modified caspase polypeptide, where the proportion of caspase polypeptide-expressing cells eliminated by apoptosis is related to the administered amount of the multimeric ligand inducer.

Provided is a method for isolating and proliferating autologous cancer antigen-specific CD8.sup.+T cells, and more particularly, a method for selecting an epitope recognized by CD8.sup.+ T cells from autologous cancer antigens present in blood of individual cancer patients; and isolating autologous cancer antigen-specific CD8.sup.+ T cells by using a peptide of the selected epitope, and a method of massively proliferating CD8.sup.+ T cells by using the method. According to the present invention, it is possible to isolate autologous cancer antigen-specific CD8.sup.+ T cells by using the peptide of the CD8 T cell epitope of the autologous cancer antigen present in blood of individual cancer patients instead of a heterologous antigen. Therefore, by using T cells recognizing the autologous cancer antigen, it is possible to effectively select and eliminate cancer cells derived from the cancer patient's own cells. Thus, T cells can be applied to treatment and alleviation of cancer diseases without side effects.