It was found that TRAIL-induced death signaling was largely diminished by lysosomal degradation system. Inhibition of lysosomal degradation by small molecules led to accumulation of DR5 in lysosomes and reversed TRAIL resistance in almost all cancer cells. Redirecting TRAIL-induced signaling away from lysosomal degradation may therefore induce massive cell death and overcome TRAIL resistance. Taking advantage of bioactive protein transduction domains (PTD) and signaling peptides, such as TAT peptide from HIV TAT protein, NLS (nuclear localization signal), MTS (mitochondrial targeting sequence), a series of new TRAILs fused with these peptides was constructed. It was found that TRAIL fused with bioactive peptide exerted remarkably high potency in inducing cell death in cancer cells, but not normal cells.

The present invention provides an adjuvant for cancer antigen peptide vaccines and virus antigen peptides, containing a pertussis vaccine as a primary ingredient. The present invention also provides a therapeutic agent for a cancer or viral infectious disease, and a prophylactic agent for metastasis or recurrence of cancer or onset of virus-induced tumor, containing a cancer antigen peptide or virus antigen peptide and a pertussis vaccine. A pertussis vaccine that can be suitably used is a whole cell body pertussis vaccine. The agents of the present invention can be safely administered in a plurality of doses.

The present invention provides methods for antigen and/or bioactive molecule delivery to antigen presenting cells utilizing ASC specks as vehicles; 1) the ASC speck composition is made of ASC protein(s) and the antigen and/or bioactive molecule(s) purified from cells as a compact micro-spherical structure; 2) purified micro-spherical ASC speck delivery vehicles are stable at 37° C. for more than 30 days; and 3) antigen and/or bioactive molecules carried by ASC specks can be efficiently phagocytosed by antigen presenting cells and their degradation in the lysosome allows antigen processing and presentation.

Methods of preventing or retarding or reversing or abolishing the onset of Parkinson's and other neurodegenerative diseases are discussed.

Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The invention relates to fragments of the Death-Domain Associated protein (DAXX protein) and of the Fas-Associated Death Domain protein (FADD protein) that inhibit cell apoptosis, in particular cell apoptosis mediated by the Fas receptor. The invention also relates to derivatives of said anti-apoptotic fragments, conjugates comprising said fragments, pharmaceutical compositions comprising said fragments, and to the medical applications of said fragments, derivatives, conjugates, and pharmaceutical compositions thereof in the treatment or prevention of diseases and conditions associated with apoptosis.

Disclosed herein is a cell death-inducing peptide that rapidly acts. The peptide is derived from Noxa protein and comprises 16 amino acid residues including MTD. The peptide is designated extended MTD (eMTD) because it contains the 10-mer MTD. eMTD rapidly exhibits potent necrotic cell death in various cell lines and, as such, can be applied to the treatment of various diseases including cancer when used in conjugation with peptides or materials for targeting specific cells.

The present invention relates to short peptides based on the amino acids sequence of the N-terminal domain of the human mitochondrial protein voltage-dependent anion channel 1 (VDAC) and to peptide conjugates having a cell permeability enhancing moiety. The peptides, peptide conjugates and pharmaceutical compositions containing them are useful for treating diseases characterized by cell hyperproliferation or resistance to cell death and in particular, cancer.

The present application provides methods of enhancing T cell function (e.g., expansion, persistence and/or effector functions), particularly by genetic modification of the Regnase-1, Batf, and additional genes (alone or in combination). The application also provides modified T cells manufactured using the methods provided by this invention and related pharmaceutical compositions. The application further provides methods of using the modified T cells for treating a disease (e.g., a cancer or an infectious disease).