The present invention relates to the prevention and treatment of disease like cancer. The inventors have previously characterized MELOE-1 antigen as an IRES dependent, melanoma specific translation product from a lncRNA mainly transcribed in the melanocytic lineage. MELOE-1 contains numerous class II epitopes and one HLA-A*0201-restricted CD8 epitope eliciting a frequent repertoire of high avidity T cells. They designed various synthetic long peptide (SLPs) comprising a CD4 epitope coupled to the CD8 epitope by a serie of linkers of 4 to 6 aa and studied the efficacy of T cell clone activation by SLP-loaded DC in vitro. Particularly, they evaluated the ability of a few selected SLPs to stimulate specific T cells proliferation of PBL from healthy donors in vitro and finally, they explored the vaccination potential of their best SLP candidate in vivo in an HLA*A0201/HLA-DRB0101 transgenic mouse. Thus, the present invention relates a SLP comprising a CD4 class II peptide linked to a CD8 class I peptide by a specific linker and its use in the treatment of disease like cancers.

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).

A vaccination method is provided. The method comprises administering to a mammal a histone deacytelase inhibitor in conjunction with a vaccine that expresses an antigen to which the mammal has a pre-existing immunity.

Materials and methods useful for generating highly mannosylated pseudotyped lentiviral vector particles comprising a Vpx protein are provided.

The invention provides CD27 agonists comprising a first component that is an anti-CD27 antibody, or antigen-binding fragment thereof, linked to a second component comprising one or more cross-linking moieties. At least one of the cross-linking moieties does not bind to an Fc receptor and the CD27 agonist stimulates T cell activity without the need for Fc receptor interaction. The cross-linking molecule(s) can be, for example, an anti-CD27, antibody, or antigen-binding fragment thereof, that can be the same or different than the first component. Alternatively, the cross-linking molecule(s) can be a CD27 ligand or a molecule (e.g., antibody) that binds a molecule on a cell such as a T cell, a tumor cell or a stromal cell. Pharmaceutical compositions comprising the CD27 agonists, and methods of using the CD27 agonists, are also provided.

The invention relates to the finding that stimulation of antigen presenting cell (APC) activation using substances such as anti-CD40 antibodies or DNA oligomers rich in non-methylated C and G (CpGs) can dramatically enhance the specific T cell response obtained after vaccination with recombinant virus like particles (VLPs) coupled, fused or otherwise attached to antigens. While vaccination with recombinant VLPs fused to a cytotoxic T cell (CTL) epitope of lymphocytic choriomeningitis virus induced low levels cytolytic activity only and did not induce efficient anti-viral protection, VLPs injected together with anti-CD40 antibodies or CpGs induced strong CTL activity and full anti-viral protection. Thus, stimulation of APC-activation through antigen presenting cell activators such as anti-CD40 antibodies or CpGs can exhibit a potent adjuvant effect for vaccination with VLPs coupled, fused or attached otherwise to antigens.

Compositions, e.g., therapeutic agents, and methods are provided for modulating gene and protein expression of Forkhead Box protein 1 (Foxp1). The therapeutic agents include short nucleic acid molecules that modulate gene and protein expression of Forkhead Box protein 1 (Foxp1) expression, viral vectors containing such molecules, T cells transduced with these viruses for adoptive therapies, and any small molecules that bind to and inactivate Foxp1. These compounds and methods have applications in cancer therapy either alone or in combination with other therapies that stimulate the endogenous immune system in the environment of the cancer, e.g., tumor.

Disclosed herein are vectors that include antigen-encoding nucleic acid sequences and co-express immune modulators. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

In one aspect, a method of treating cancer in a mammal is provided. The method comprises administering to the mammal an oncolytic vector that expresses a tumour antigen to which the mammal has a pre-existing immunity. In another aspect, a method of boosting immune response in a mammal having a pre-existing immunity to an antigen is provided comprising intravenous administration to the mammal of a B-cell infecting vector that expresses the antigen.

Materials and methods useful for generating highly mannosylated pseudotyped lentiviral vector particles comprising a Vpx protein are provided.