STABILIZED CHIMERIC SYNTHETIC PROTEINS AND THERAPEUTIC USES THEREOF
The disclosure relates to compositions and methods for treating disease. More particularly, the disclosure relates to stabilized chimeric synthetic proteins and their use for treating cancer.
1 . A chimeric synthetic protein, comprising:
a chimeric polypeptide sequence;
at least one linker, and
a polypeptide sequence.
2 . The chimeric synthetic protein according to claim 1 , wherein the polypeptide sequence includes an immunogenic polypeptide sequence.
3 . The chimeric synthetic protein according to claim 1 , wherein the polypeptide sequence includes a cholera toxin B (CT-B) protein.
4 . The chimeric synthetic protein according to claim 1 , wherein the at least one linker includes a first linker that separates the chimeric polypeptide sequence from the polypeptide sequence.
5 . The chimeric synthetic protein according to claim 4 , wherein the first linker is selected from the group consisting of SSG, GSSG, SSGGG, SGG, GGSGG, GGGGS, SSGGGSGG, SSGGGGSGGG, TSGGGSG, TSGGGGSGG, SSGGSGGGSG, SSGGGSGGS SG, GGSGGTSGGGSG, SGGTSGGGGSGG, GGSGGTSGGGGSGG, SSGGGGSGGGSSG, SSGGGSGGSSGGG, and SSGGGGSGGGSSGGG.
6 . The chimeric synthetic protein according to claim 4 , wherein the first linker is SSGGSGGGSG.
7 . The chimeric synthetic protein according to claim 1 , wherein the chimeric polypeptide sequence includes a vascular endothelial growth factor (VEGF) sequence.
8 . The chimeric synthetic protein according to claim 1 , wherein the chimeric polypeptide sequence includes a VEGF sequence selected from the group consisting of VEGF-A, VEGF-B, VEGF-C, VEGF-D, and combinations thereof.
9 . The chimeric synthetic protein according to claim 8 , wherein the chimeric polypeptide sequence includes a first VEGF domain and a second VEGF domain.
10 . The chimeric synthetic protein according to claim 9 , wherein the first VEGF domain includes VEGF-D, or a portion thereof, and the second VEGF domain includes VEGF-A, or a portion thereof.
11 . The chimeric synthetic protein according to claim 10 , wherein the first VEGF domain is TFYDIETLKVIDEEWQRTQ and the second VEGF domain is CHPIETLVDIFQEYPDEIEYIFKPSCVPLMRCGGCCNDEG.
12 . The chimeric synthetic protein according to claim 9 , wherein the chimeric polypeptide sequence binds to a vascular endothelial growth factor receptor (VEGFR) selected from the group consisting of VEGFR-1, VEGFR-2, VEGFR-3, and combinations thereof.
13 . The chimeric synthetic protein according to claim 12 , wherein the chimeric polypeptide sequence binds to VEGFR-1, VEGFR-2, and VEGFR-3.
14 . The chimeric synthetic protein according to claim 1 , wherein the chimeric synthetic protein initially has an amino acid sequence of
MTPQNITDLCAEYHNTQIHTLNDKIFSYTESLAGKREMAIITFKNGATFQVEV
DSQKKAIERMKDTLRIAYLTEAKVEKLCVWNNKTPHAIAAISMANSSGGSGGG
PGSQHISGTFYDIETLKVIDEEWQRTQCHPIETLVDIFQEYPDEIEYIFKPSC
VPLMRCGGCCNDEG.
15 . The chimeric synthetic protein according to claim 14 , wherein the initial chimeric synthetic protein is processed to have an amino acid sequence of
TPQNITDLCAEYHNTQIHTLNDKIFSYTESLAGKREMAIITFKNGATFQVEVP
GSQHIDSQKKAIERMKDTLRIAYLTEAKVEKLCVWNNKTPHAIAAISMANSSG
GSGGGSGTFYDIETLKVIDEEWQRTQCHPIETLVDIFQEYPDEIEYIFKPSCV
PLMRCGGCCNDEG.
16 . An immunogenic composition, comprising:
a chimeric polypeptide sequence;
at least one linker, and
a polypeptide sequence.
17 . The immunogenic composition according to claim 16 , wherein the polypeptide sequence includes an immunogenic polypeptide sequence.
18 . The immunogenic composition according to claim 16 , wherein the polypeptide sequence includes a cholera toxin B (CT-B) protein.
19 . The immunogenic composition according to claim 16 , wherein the at least one linker includes a first linker that separates the chimeric polypeptide sequence from the polypeptide sequence.
20 . The immunogenic composition according to claim 16 , wherein the first linker is selected from the group consisting of SSG, GSSG, SSGGG, SGG, GGSGG, GGGGS, SSGGGSGG, SSGGGGSGGG, TSGGGSG, TSGGGGSGG, SSGGSGGGSG, SSGGGSGGSSG, GGSGGTSGGGSG, SGGTSGGGGSGG, GGSGGTSGGGGSGG, SSGGGGSGGGSSG, SSGGGSGGSSGGG, and SSGGGGSGGGSSGGG.
21 . The immunogenic composition according to claim 20 , wherein the first linker is SSGGSGGGSG.
22 . The immunogenic composition according to claim 16 , wherein the chimeric polypeptide sequence includes a vascular endothelial growth factor (VEGF) sequence.
23 . The immunogenic composition according to claim 16 , wherein the chimeric polypeptide sequence includes a VEGF sequence selected from the group consisting of VEGF-A, VEGF-B, VEGF-C, VEGF-D, and combinations thereof.
24 . The immunogenic composition according to claim 16 , wherein the chimeric polypeptide sequence includes a first VEGF domain and a second VEGF domain.
25 . The immunogenic composition according to claim 24 , wherein the first VEGF domain includes VEGF-D, or a portion thereof, and the second VEGF domain includes VEGF-A, or a portion thereof.
26 . The immunogenic composition according to claim 25 , wherein the first VEGF domain is TFYDIETLKVIDEEWQRTQ and the second VEGF domain is CHPIETLVDIFQEYPDEIEYIFKPSCVPLMRCGGCCNDEG.
27 . The immunogenic composition according to claim 26 , wherein the chimeric polypeptide sequence binds to a vascular endothelial growth factor receptor (VEGFR) selected from the group consisting of VEGFR-1, VEGFR-2, VEGFR-3, and combinations thereof.
28 . The immunogenic composition according to claim 27 , wherein the chimeric polypeptide sequence binds to VEGFR-1, VEGFR-2, and VEGFR-3.
29 . The immunogenic composition according to claim 16 , wherein the synthetic protein chimeric synthetic protein initially has an amino acid sequence of
MTPQNITDLCAEYHNTQIHTLNDKIFSYTESLAGKREMAIITFKNGATFQVEV
PGSQHIDSQKKAIERMKDTLRIAYLTEAKVEKLCVWNNKTPHAIAAISMANSS
GGSGGGSGTFYDIETLKVIDEEWQRTQCHPIETLVDIFQEYPDEIEYIFKPSC
VPLMRCGGCCNDEG.
30 . The immunogenic composition according to claim 16 , wherein the initial chimeric synthetic protein is processed to have an amino acid sequence of
TPQNITDLCAEYHNTQIHTLNDKIFSYTESLAGKREMAIITFKNGATFQVEVP
GSQHIDSQKKAIERMKDTLRIAYLTEAKVEKLCVWNNKTPHAIAAISMANSSG
GSGGGSGTFYDIETLKVIDEEWQRTQCHPIETLVDIFQEYPDEIEYIFKPSCV
PLMRCGGCCNDEG.
31 . The immunogenic composition according to claim 16 , further comprising an adjuvant.
32 . A method of treating a patient in need thereof, comprising:
administering to the patient the immunogenic composition of claim 16 in a same day or at alternate days or times during a vaccination period.
33 . The method of claim 32 , wherein the patient has a cancer.