Compositions and methods for cancer immunotherapy
View Patent ↗The present invention provides a combination therapy which relies on a small molecule immune stimulator—cyclic-di-nucleotide (CDN)—that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes) formulated with allogeneic human tumor cell lines engineered to secrete high amounts of GM-CSF. This combination therapy can provide an ideal synergy of multiple tumor associated antigens, DC recruitment and proliferation, coupled with a potent DC activation stimulus.
1. A composition comprising:
a cyclic purine dinucleotide which binds to STING and induces STING-dependent TBK1 activation; and
an inactivated tumor cell which expresses and secretes granulocyte-macrophage colony-stimulating factor (GM-CSF).
2. A composition according to claim 1 , further comprising a pharmaceutically acceptable excipient.
3. A composition according to claim 1 , wherein the tumor cell is inactivated by treatment with radiation.
4. A composition according to claim 1 , wherein the cyclic purine dinuclotide is selected from the group consisting of c-di-AMP, c-di-GMP, c-di-IMP, c-AMP-GMP, c-AMP-IMP, and c-GMP-IMP, or combinations thereof.
5. A composition according to claim 1 , wherein the cyclic purine dinuclotide is formulated with one or more lipids.
6. A composition according to claim 5 , wherein the cyclic purine dinuclotide is formulated with digitonin.
7. A composition according to claim 5 , wherein the one or more lipids form a liposome.
8. A composition according to claim 1 , further comprising one or more adjuvants.
9. A composition according to claim 8 , wherein the one or more adjuvants comprise CpG and/or monophosphoryl lipid A.