Composition comprising a nucleotide sequence encoding an ELA2 fusion protein and plasmacytoid dendritic cells
View Patent ↗The present invention refers to a novel combination of nucleotide and cellular vaccine composition and pharmaceutical composition and use thereof for treating and/or preventing diseases, including infectious diseases, cancer, autoimmune diseases, allergy, diabetes and blood disorders. The vaccine composition comprises a nucleotide sequence encoding an antigenic molecule and gene-modified antigen-presenting cells (APCs), preferably provided as an intermixture. The APCs are modified to express immune modulating molecules. Immunization with the vaccine composition of present invention into a subject, induces the host immune system to respond and generate efficient immunity against either pre-existing disease or protect the host against the disease.
1. A therapeutic composition, comprising an incubated combined mixture of:
(a) a first component selected from (i) a nucleic acid having a nucleotide sequence encoding a tumor associated antigen, wherein the tumor-associated antigen is the e1a2 fusion peptide of SEQ ID NO: 4, said nucleic acid is provided in a plasmid vector and under transcriptional control of a promoter, and said plasmid vector comprises an unmethylated cytidine phosphate guanosine (CpG) sequence, (ii) acute leukemia tumor lysate, and (iii) the e1a2 fusion peptide of SEQ ID NO: 5; and
(b) a second component comprising plasmacytoid dendritic cells expressing Toll-like receptor 9 and modified for stable expression of CD40 ligand or GM-CSF by a nucleotide sequence engineered into said professional antigen-presenting cells, provided that when the plasmacytoid dendritic cells are modified for stable expression of GM-CSF, then the first component is (ii) acute leukemia tumor lysate.
2. The composition according to claim 1 , wherein the first component is (i) a nucleic acid having a nucleotide sequence encoding a tumor associated antigen, wherein the tumor-associated antigen is the e1a2 fusion peptide of SEQ ID NO: 4, said nucleic acid is provided in a plasmid vector and under transcriptional control of a promoter, and said plasmid vector comprises an unmethylated cytidine phosphate guanosine (CpG) sequence.
3. The composition according to claim 1 , wherein the first component is (ii) acute leukemia tumor lysate.
4. The composition according to claim 3 , wherein the second component comprises plasmacytoid dendritic cells expressing Toll-like receptor 9 and modified for stable expression of CD40 ligand.
5. The composition according to claim 3 , wherein the second component comprises plasmacytoid dendritic cells expressing Toll-like receptor 9 and modified for stable expression of GM-CSF.
6. The composition according to claim 1 , wherein the first component is (iii) the e1a2 fusion peptide of SEQ ID NO: 5.
7. The composition of claim 1 , wherein the first component is (ii) acute leukemia tumor lysate comprising Philadelphia chromosome-positive tumor lysate.