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 pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular against Preferentially Expressed Antigen of Melanoma (PRAME). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Disclosed provides a method of treating measure residue disease (MRD) in a subject with cancer using an allogeneic leukemia-derived cell as a vaccine based on the information provided by prognostic biomarkers comprising dendritic cells including cDC1 cDC2, and/or pDC; CD8+ T cells including CD8+CD45RA+ cells, CD8+CD45RA? CCR7+CM T cells, and/or CD8 RO+ T cells; B cells; NK cells including CD56++NK cells and/or CD56+NK cells; CD4 CD161+ T cells; CD14+CD16? non-inflammatory monocytes, or any combination thereof.

The present invention relates to the field of biotechnology. Specifically, the invention provides antigen-specific T-cell receptors (TCRs). Further, the invention encompasses polynucleotides encoding the same and vectors comprising said polynucleotides. Host cells comprising the molecules of the invention are also provided. Moreover, the invention provides means and methods for diagnostics and therapy, in particular of cancer.

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 an isolated cell composition suitable for adoptive immunotherapy, as well as methods of manufacturing the cell compositions and methods of treatment with the cell compositions. The composition comprises, in a pharmaceutically acceptable carrier, at least about 10.sup.6 CD8+ T cells specific for target peptide antigen(s). In various embodiments, the composition is predominately CD8+ T cells, and at least about 20% of T cells in the composition exhibit a central or effector memory phenotype, providing for a robust and durable adoptive therapy from a natural T cell repertoire that has undergone natural selection.

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 relates to the combination of a T cell receptor (TCR) specific for the FRAME peptide SLLQH-LIGL and a chimeric co-stimulatory receptor comprising an extracellular domain derived from PD-1(CD279) and an intracellular domain derived from 4-1BB (CD137). In particular, the invention refers to a cell comprising said TCR and chimeric co-stimulatory protein. Further the invention refers to a nucleic acid encoding the TCR and the co-stimulatory receptor, a corresponding vector and a corresponding nucleic acid composition. Moreover, the invention relates to the according pharmaceutical composition. Accordingly the invention also relates to the cell and the nucleic acid constructs for use as a medicament, in particular to the TCR for use in the treatment of cancer.

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular against Preferentially Expressed Antigen of Melanoma (PRAME). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Embodiments of the disclosure include methods and compositions in which NK cells are modified by the hand of man to express the T-cell receptor and CD3 co-receptor on NK cells that do not naturally express them. Such modified NK cells work effectively with bispecific or multi-specific antibodies that are tailored to comprise anti-CD3 antibodies that bind the modified NK cells, thereby triggering signaling, activation, and cytotoxicity of target cells to which the antibodies also bind. Thus, the NK cells are specifically configured to be able to work effectively with Bispecific NK cell engagers (BiKEs) as well as Bispecific T cell Engagers (BiTEs).