Provided herein are immunogenic compositions comprising a recombinant modified vaccinia virus Ankara (MVA) comprising a nucleic acid sequence encoding a CD40 ligand (CD4OL) and a nucleic acid sequence encoding a heterologous disease-associated antigen, wherein the immunogenic composition induces increases T-cell immune responses specific for the heterologous disease-associated antigen when administered to a human host, and related methods and uses.

The present invention relates to a pharmaceutical composition comprising, as an active ingredient, a fusion protein in which a tissue-penetrating peptide is fused to an anti-vascular endothelial growth factor agent, methods of treating eye diseases with the pharmaceutical composition, and a method for preparing an anti-VEGF agent with an improved efficacy and ability to overcome resistance.

An object of the present invention is to provide an antibody having significantly high affinity for VEGF compared to the prior art. The present invention provides a monoclonal antibody against VEGF, which binds to a vascular endothelial growth factor (VEGF) with a dissociation constant of 1×10.sup.−11 mol/L or less.

Provided herein are immunogenic compositions comprising a recombinant modified vaccinia virus Ankara (MVA) comprising a nucleic acid sequence encoding a CD40 ligand (CD40L) and a nucleic acid sequence encoding a heterologous disease-associated antigen, wherein the immunogenic composition induces increases T-cell immune responses specific for the heterologous disease-associated antigen when administered to a human host, and related methods and uses.

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.

An object of the present invention is to provide an antibody having significantly high affinity for VEGF compared to the prior art. The present invention provides a monoclonal antibody against VEGF, which binds to a vascular endothelial growth factor (VEGF) with a dissociation constant of 1×10.sup.−11 mol/L or less.

The present invention relates to an immunostimulatory composition comprising a) an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a cationic or polycationic compound, and b) at least one free mRNA, encoding at least one therapeutically active protein, antigen, allergen and/or antibody, wherein the immunostimulatory composition is capable to elicit or enhance an innate and optionally an adaptive immune response in a mammal. The inventive immunostimulatory composition may be a pharmaceutical composition or a vaccine. The invention furthermore relates to a method of preparation of the inventive immunostimulatory composition. The invention also relates to the use of the inventive immunostimulatory composition or its components (for the preparation of a pharmaceutical composition or a vaccine) for the treatment of various diseases. Finally, the invention relates to kits containing the inventive immunostimulatory composition, its components and/or the pharmaceutical composition or vaccine.

The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.

The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.

The present invention relates to a pharmaceutical composition comprising, as an active ingredient, a fusion protein in which a tissue-penetrating peptide is fused to an anti-vascular endothelial growth factor agent, methods of treating eye diseases with the pharmaceutical composition, and a method for preparing an anti-VEGF agent with an improved efficacy and ability to overcome resistance.