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.

Disclosed herein are lymphocytes for use in adoptive cell transfer that have chemically- or genetically-inhibited Sirt2 expression. Also disclosed are methods of inhibiting or ablating Sirt2 expression in a T cell ex vivo. Also disclosed are methods of treating cancer in a subject that involves collecting lymphocytes, such as tumor infiltrating lymphocytes (TILs), from the subject, treating the lymphocytes ex vivo to inhibit Sirt2 expression, and transferring the modified lymphocytes back to the subject.

The present invention relates to nanoparticles complexed with biomacromolecule agents configured for treating, preventing or ameliorating various types of disorders, and methods of synthesizing the same. In particular, the present invention is directed to compositions comprising nanoparticles (e.g., synthetic high density lipoprotein (sHDL)) carrying biomacromolecule agents (e.g., nucleic acid, peptides, glycolipids, etc.), methods for synthesizing such nanoparticles, as well as systems and methods utilizing such nanoparticles (e.g., in diagnostic and/or therapeutic settings).

Provided herein are interleukin-13 receptor α2 peptide-based brain cancer vaccines and methods for treating and vaccinating against brain cancer comprising administering to patients in need thereof interleukin-13 receptor α2 peptide-based brain cancer vaccines. Also provided herein are regimens comprising interleukin-13 receptor α2 peptides and at least one additional peptide and/or immunostimulant.

The present invention relates to nucleic acids and peptides encoded by those nucleic acids. In particular, the peptides comprise a modified IgG1 Fc region and one or more heterologous epitopes, which may be B- or T-cell epitopes. A nucleic acid of the invention may encode a polypeptide comprising: (i) a modified Fc region of a human IgG1, and (i) at least one heterologous antigen, wherein (a) the modified Fc region comprises at least the part of Fc that is capable of binding to CD64 and/or TRIM21, (b) at least one residue of the Fc region is modified to the corresponding residue from a mouse IgG3 antibody and (c) the modified Fc region has enhanced avidity for Fc-gamma receptor (FcγR) when compared to the corresponding wildtype Fc region.

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences having multiple repeats of distinct epitope-encoding sequences or having antigen-encoding nucleic acid sequences having less than 700 nucleotides and encoding multiple distinct epitope-encoding sequences. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines.

Disclosed herein are compositions and methods for treating cancer and in particular vaccines that treat and provide protection against tumor growth.

The disclosure is related to compositions comprising a cell and a spherical nucleic acid (SNA) comprising a nanoparticle, an oligonucleotide on the surface of the nanoparticle, and an antigen; and to methods for production of such compositions and their applications, including but not limited to adoptive cell therapy.

This document provides methods and materials for expanding antigen-specific T cells (e.g., antigen-specific CD4.sup.+ T cells and/or antigen-specific CD8.sup.+ T cells) in culture. For example, methods and materials for performing a polyclonal stimulation step for a particular duration (e.g., from about 1 hour to about 48 hours) to increase the expansion of T cells having a desired antigen specificity are provided.

Disclosed herein are compositions and methods for treating cancer and in particular vaccines that treat and provide protection against tumor growth.