Combination immunotherapies comprising IL-15 superagonists
Methods and compositions for generating enhanced immune responses using adenovirus vectors that allow for multiple vaccinations in combination with an IL-15 superagonist complex in subjects in need thereof are provided.
1. A composition comprising a first recombinant adenovirus subtype 5 (Ad5) vector comprising a deletion in an E1 gene region, a deletion in an E2b gene region, and a nucleic acid sequence encoding a carcinoembryonic antigen (CEA) according to SEQ ID NO:3 or SEQ ID NO:4, and:
a) a second recombinant adenovirus vector comprising a nucleic acid sequence encoding an IL-15N72D domain of a human interleukin-15 (IL-15) superagonist complex and an IL-15RaSu/Fc fusion domain of the IL-15 superagonist complex; or
b) a third recombinant adenovirus vector comprising a nucleic acid sequence encoding an IL-15N72D domain of a human IL-15 superagonist complex and fourth recombinant adenovirus vector comprising a nucleic acid sequence encoding an IL-15RαSu/Fc fusion domain of the IL-15 superagonist complex.
2. The composition of claim 1 , wherein the CEA is SEQ ID NO: 3.
3. The composition of claim 1 , wherein the nucleic acid sequence encoding CEA is SEQ ID NO: 1 or SEQ ID NO: 100.
4. The composition of claim 1 , wherein the CEA is SEQ ID NO:4.
5. The composition of claim 1 , wherein the IL-15 superagonist complex is ALT-803.
6. The composition of claim 1 , wherein the composition comprises at least 1×10 9 viral particles in a single dose.
7. The composition of claim 6 , wherein the composition comprises 1×10 9 -5×10 12 viral particles in a single dose.
8. The composition of claim 7 , wherein the composition comprises 1×10 10 -5×10 12 viral particles in a single dose.
9. The composition of claim 8 , wherein the composition-comprises 1×10 10 -5×10 11 viral particles in a single dose.