PD1-based vaccination composition and methods thereof
Provided herein is DNA vaccine and composition comprising PD1-based TWIST1. Also provided is a method for inducing TWIST1-specific T cell response by administering a PD1-based TWIST1 vaccine. Also provided is a method for inducing TWIST1-specific T cell response by administering a PD1-based TWIST1 vaccine and an immune checkpoint inhibitor.
1 . A DNA vaccine construct encoding a fusion protein comprising soluble PD1 linked with TWIST1, and wherein the fusion protein comprises a TWIST1 peptide consisting of the amino acid sequence of SEQ ID NO: 4.
2 . The DNA vaccine construct of claim 1 further comprising a linker.
3 . The DNA vaccine construct of claim 2 further comprising a tissue plasminogen activator (tPA).
4 . A composition comprising a DNA vaccine construct encoding a fusion protein comprising: (i) a soluble PD1; and (ii) TWIST1, wherein the soluble PD1 is linked to the TWIST1; and an acceptable pharmaceutical carrier, and wherein the fusion protein comprises a TWIST1 peptide consisting of the amino acid sequence of SEQ ID NO: 4.
5 . A kit comprising a DNA vaccine construct encoding a fusion protein comprising (i) a soluble PD1; and (ii) TWIST1, wherein the soluble PD1 is linked to the TWIST1; and an acceptable pharmaceutical carrier, and wherein the fusion protein comprises a TWIST1 peptide consisting of the amino acid sequence of SEQ ID NO: 4.
6 . A method for inducing TWIST1-specific T cell response in a subject having TWIST1 overexpressed cancer, comprising administering to the subject an effective amount of a DNA vaccine comprising a DNA construct encoding a fusion protein comprising soluble PD1 linked with TWIST1, wherein the fusion protein comprises a TWIST1 peptide consisting of the amino acid sequence of SEQ ID NO: 4.
7 . The method of claim 6 wherein the method is effective in controlling the invasion and metastasis of the TWIST1 overexpressed cancer.
8 . The method of claim 6 wherein the TWIST1 overexpressed cancer is selected from the group consisting of mesothelioma, AB1 mesothelioma, 4T1 breast cancer, melanoma, colon cancer, prostate cancer, and gastric carcinomas.
9 . The method of claim 6 further comprising administering an immune checkpoint inhibitor to the subject.
10 . The method of claim 9 wherein the immune checkpoint inhibitor is an anti-CTLA-4 antibody.
11 . The method of claim 6 wherein the effective amount of the DNA vaccine construct is 100 μg-200 mg.
12 . The method of claim 11 wherein the DNA vaccine is administered intramuscularly at 10 days to three-week intervals for three times.
13 . The method of claim 10 wherein the anti-CTLA-4 antibody is administered at a dose of 200 μg-400 mg.
14 . The method of claim 13 wherein the anti-CTLA-4 antibody is administered intraperitoneally 24 hours after administration of the DNA vaccine and every 4 days for three times.