Tumor-specific peptide antigens for ovarian cancer and uses thereof
Ovarian cancer, notably high-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from recent progress in cancer immunotherapy. While HGSC infiltration by lymphocytes correlates with superior survival, the nature of antigens that can elicit anti-HGSC immune responses is unknown. Novel tumor-specific antigens (TSAs) shared by a large proportion of ovarian tumors are described herein. Most of the TSAs (>80%) described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells and vaccines derived from these TSAs are described. The use of the TSAs, nucleic acids, compositions, cells and vaccines for the treatment of ovarian cancer is also described.
1 . A method of stimulating a T cell response against ovarian cancer in a subject comprising administering to the subject an effective amount of
(a) one or more tumor antigen peptides of 15 amino acids or less comprising one or more of the amino acid sequences set forth in SEQ ID NOs: 1-103; or
(b) one or more nucleic acids encoding the one or more tumor antigen peptides defined in (a).
2 . The method of claim 1 , wherein said ovarian cancer is a serous carcinoma.
3 . The method of claim 2 , wherein said serous carcinoma is high-grade serous carcinoma (HGSC).
4 . The method of claim 1 , further comprising administering at least one additional antitumor agent or therapy to the subject.
5 . The method of claim 4 , wherein said at least one additional antitumor agent or therapy is a chemotherapeutic agent, immunotherapy, an immune checkpoint inhibitor, radiotherapy or surgery.
6 . The method of claim 1 , wherein the one or more tumor antigen peptides or nucleic acids, are formulated in a pharmaceutical composition that further comprises at least one pharmaceutically acceptable excipient or carrier.
7 . The method of claim 6 , wherein the at least one pharmaceutically acceptable excipient or carrier comprises a lipid vehicle.
8 . The method of claim 6 , wherein the at least one pharmaceutically acceptable excipient or carrier comprises a vaccine adjuvant.
9 . The method of claim 1 , wherein the one or more tumor antigen peptides comprise the amino acid sequence set forth in SEQ ID NO: 36, SEQ ID NO: 88, SEQ ID NO: 102 and/or SEQ ID NO: 103.
10 . The method of claim 1 , wherein the method comprises administering to the subject an effective amount of one or more nucleic acids encoding the one or more tumor antigen peptides defined in (a).
11 . The method of claim 10 , wherein the one or more nucleic acids are mRNA molecules.
12 . The method of claim 9 , wherein the method comprises administering to the subject an effective amount of one or more nucleic acids encoding the one or more tumor antigen peptides comprising the amino acid sequence set forth in SEQ ID NO: 36, SEQ ID NO: 88, SEQ ID NO: 102 and/or SEQ ID NO: 103.
13 . The method of claim 12 , wherein the one or more nucleic acids are mRNA molecules.
14 . The method of claim 11 , wherein the one or more mRNA molecules are admixed with a lipid vehicle.
15 . The method of claim 13 , wherein the one or more mRNA molecules are admixed with a lipid vehicle.
16 . The method of claim 1 , wherein the method further comprises administering to the subject an effective amount of
(i) one or more tumor antigen peptides of 15 amino acids or less comprising one or more of the amino acid sequences set forth in SEQ ID NOs: 104-111; or
(ii) one or more nucleic acids encoding the one or more tumor antigen peptides defined in (i).
17 . The method of claim 16 , wherein the method comprises administering to the subject an effective amount of one or more nucleic acids encoding the one or more tumor antigen peptides defined in (i).
18 . The method of claim 17 , wherein the one or more mRNA molecules are admixed with a lipid vehicle.
19 . The method of claim 18 , wherein the one or more mRNA molecules are admixed with a lipid vehicle.