Cancer vaccines and methods of delivery
Disclosed are compositions, methods, and kits for treating a cancer or pre-cancer. In particular, the invention generally relates to cancer vaccines as well as methods of delivering the vaccines. Combination treatments including the vaccines in combination with immunomodulatory agents are also contemplated.
1. A method of treating a HER3-expressing cancer or precancer or of reducing the likelihood of the cancer developing resistance to a cancer therapeutic or prevention agent in a subject comprising:
a) administering to the subject a therapeutically effective amount of a first dose of a minicircle DNA comprising first polynucleotide encoding an antigenic polypeptide comprising the extracellular domain of HER3 (amino acids 1-643 of SEQ ID NO: 2), wherein the first polynucleotide is circular and lacks a bacterial origin of replication and an antibiotic resistance gene;
b) administering to the subject a therapeutically effective amount of a second dose of the minicircle DNA; and
c) subsequently administering to the subject a therapeutically effective amount of an adenoviral vaccine vector encoding the antigenic polypeptide;
wherein the method produces an extended anti-HER3 cellular immune response.
2. The method of claim 1 , wherein the minicircle DNA comprises a polynucleotide construct comprising a heterologous promoter operably connected to a first polynucleotide encoding the extracellular domain of HER3 fused to the C1C2 domains of lactadherin comprising SEQ ID NO:12.
3. The method of claim 1 , wherein steps a)-c) are performed before administration of the cancer therapeutic or prevention agent.
4. The method of claim 1 , wherein the cancer therapeutic or prevention agent is an agent targeting HER2, HER1, estrogen receptor, EGFR, or IGF1R.
5. The method of claim 1 , further comprising administering a checkpoint inhibitor immunomodulatory agent and wherein the DNA vaccine and the vaccine vector composition are administered concurrently with, before or after administration of the checkpoint inhibitor immunomodulatory agent.
6. The method of claim 1 , wherein the cancer or precancer is selected from a breast, prostate, lung, ovarian, colon, rectal, pancreas, bladder, head and neck or liver cancer or precancer.
7. The method of claim 1 , wherein the subject is human.