Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.

The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising disrupted T cell receptor and/or HLA and comprising a chimeric antigen receptor. In certain embodiments, the compositions are employed allogeneically as universal reagents for “off-the-shelf” treatment of medical conditions such as cancer, autoimmunity, and infection. In particular embodiments, the T cell receptor-negative and/or HLA-negative T cells are generated using zinc finger nucleases, for example.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided.

Disclosed are immunotherapeutic compositions and the concurrent use of combinations of such compositions for the improved induction of therapeutic immune responses and/or for the prevention, amelioration and/or treatment of disease, including, but not limited to, cancer and infectious disease.

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.

The present application provides methods of preparing tumor antigen-specific T cells comprising enriching activated T cells from a first co-culture comprising a first population of antigen-loaded dendritic cells loaded and a population of T cells, and co-culturing the enriched activated T cells with a second population of antigen-loaded dendritic cells. Also provided are methods of treating cancer in an individual using the tumor antigen-specific T cells, pharmaceutical compositions and kits for cell-based cancer immunotherapy.

The present invention concerns compositions and methods related to approaches to render ineffective Th1 T cells resistant to the inhibitory cytokine milieu present in a cancer microenvironment. In particular embodiments, tumor-specific T cells are modified to employ a chimeric receptor that binds inhibitory/suppressive cytokines and converts their intracellular consequences to a Th1 immunostimulaotyr/activating signal. In specific embodiments, the T cells employ a chimeric antigen receptor having exodomains for IL10, IL13 and/or IL4 fused with the signal transducing endodomains for IL2 and/or IL7.

Described herein is a method of preventing or treating a disease in a mammalian subject, comprising administering to the subject who is in need thereof an effective dosage of a pharmaceutical composition comprising a virus like particle (VLP) comprising: an alphavirus replicon comprising a recombinant polynucleotide, wherein the polynucleotide comprises a sequence encoding both subunits of a human class II major histocompatibility antigen, a retroviral gag protein, and a fusogenic envelope protein, wherein the VLP does not contain an alphavirus structural protein gene.

The success of anti-tumor immune responses requires effector T cells to infiltrate solid tumors, a process guided by chemokines. Herein, we demonstrate that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10, and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide the first direct in vivo evidence for controlling lymphocyte trafficking through CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing the biologically active form of chemokines as a strategy to enhance tumor immunotherapy.