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.

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for Kita-Kyushu Lung Cancer Antigen 1.sub.52-60 (KK-LC-1.sub.52-60). Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

The present invention relates to an adoptive T cell therapy using cells generated by genetically or biochemically reprogramming T cells to produce T memory stem cells (Tscm) that persist longer in vivo and are superior anti-tumor effector cells.

Methods and compositions for inducing CD8+ T cells to express a CD62L.sup.hiCD44.sup.lo na?ve-like phenotype are provided. One embodiment provides a pharmaceutical composition containing CD8+ T cells induced to express a CD62L.sup.hiCD44.sup.lo na?ve-like phenotype and optionally an excipient. The CD8+ T cells can be induced by contacting them with an effective amount of a MEK1/2 inhibitor. An exemplary MEK1/2 inhibitor is Selumetinib. The induced CD8+ cells can be used to treat cancer, reduce tumor burden, or treat infections in a subject in need thereof.

Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.

The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, GATA3 and/or FOXO1 modulation are provided for use as markers, marker signatures and molecular targets. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, POU2AF1 modulation is provided for use as a marker, marker signature and molecular target. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

Described herein are organoids that include at least one type of immune cell along with systems and devices including the same. Methods of preparing and using such organoids, devices and systems are also described herein.

The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.

The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.