Provided herein are methods for delaying or inhibiting T cell maturation or differentiation in vitro for a T cell therapy, comprising contacting one or more T cells from a subject in need of a T cell therapy with an AKT inhibitor and at least one of exogenous Interleukin-7 (IL-7) and exogenous Interleukin-15 (IL-15), wherein the resulting T cells exhibit delayed maturation or differentiation. In some embodiments, the method further comprises administering the one or more T cells to a subject in need of a T cell therapy.

Embodiments of the disclosure include methods and compositions for enhancing expansion of immune cells for immunotherapy. In particular embodiments, immune cells, such as T-cells, express a constitutively active cytokine receptor in which the transmembrane and endodomains are able to provide an activating signal separately from any input to the corresponding exodomain to which they are operably linked. In specific embodiments, the transmembrane and endodomain from IL-7R is utilized with the exodomain of CD34.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present disclosure relates, at least in part, to mycobacterial polynucleotides and polypeptides, to fragments or variants thereof, to cells comprising the mycobacterial polynucleotides and polypeptides, to cells comprising the mycobacterial polynucleotides and polypeptides, that are engineered to expand T-cells ex vivo, and to methods of use thereof.

Production and use of novel therapeutic cells, called T-Vehicles, in the allogeneic Adoptive Cell Therapy setting allows a wide range of therapeutic benefits to accrue with minimal or no risk of GVHD. T-Vehicles are created from donor T cells that are altered to contain therapeutic attributes that do not include their native antigen receptors and can deliver therapeutic benefits irrelevant of their native antigen specificity. T-Vehicles can possess highly restricted native antigen specificity that renders them unable to recognize antigens present on normal cells and incapable of initiating GVHD, making them ideal transport vehicles to deliver various therapeutic attributes in vivo. In essence, production and use of T-Vehicles is a paradigm shift that opens the door to therapeutic application of T cells in ways not previously contemplated, independent of whether or not there is an HLA match between the donor and the recipient.

Disclosed is a T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of human papillomavirus (HPV) 16 E6, E6.sub.29-38. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of a condition in a mammal and methods of treating or preventing a condition in a mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells.

Embodiments of the disclosure concern methods of identifying whether or not antigens from a particular pathogen are immunogenic, including the order of their immunogenicity. Other embodiments concern correlations between attributes of T cells and their clinical efficacy, such as mathematical representations thereof.

Provided herein are chimeric antigen receptors (CAR) that include a spacer sequence that provides for a cell-to-cell distance between a cell expressing the CAR and a target cell. Embodiments are provided in which an extracellular element of CARs include a spacer sequence, wherein, when the CAR is expressed on the surface of a cell, a cell-to-cell distance between the CAR expressing cell and a target expressing cell is between about 17 nm to about 25 nm, inclusive of the endpoints.

The disclosure relates generally to methods and compositions for performing bone marrow transplants using a non-myeloablative chemotherapeutic agent and chemotherapeutic-resistant cells. Using the methods and compositions described herein, a patient's bone marrow may be reconstituted and the patient avoids adverse side effects, including myeloablation and/or an impaired immune system.