Compositions and methods for treating cancer and promoting wound healing
Protein complex variants, compositions, and methods of use thereof are provided. The protein complex variant includes a cholera toxin B subunit variant having one or more modifications thereto. The method of use thereof includes treating a disease by administering an effective amount of a composition including a cholera toxin B subunit variant to a subject in need thereof.
1. A method of promoting mucosal wound healing, comprising administering to a subject in need thereof an effective amount of a cholera toxin B subunit variant comprising an endoplasmic reticulum (ER) retention sequence attached to its C-terminus.
2. The method of claim 1 , wherein the C-terminal ER retention sequence comprises a hexapeptide sequence.
3. The method of claim 1 , wherein the C-terminal ER retention sequence comprises SEKDEL (SEQ ID NO: 30), KDEL (SEQ ID NO: 31), or HDEL (SEQ ID NO: 32).
4. The method of claim 1 , wherein the C-terminal ER retention sequence comprises KDEL (SEQ ID NO: 31).
5. The method of claim 1 , wherein the cholera toxin B subunit variant further comprises an Asn4 to Ser mutation.
6. The method of claim 1 , wherein the cholera toxin B subunit variant further comprises a secretory signal peptide selected from a rice alpha-amylase secretory signal peptide, a Nicotiana plumbagenifolia calreticulin secretory signal peptide, an apple pectinase secretory signal peptide, or a barley alpha-amylase secretory signal peptide.
7. The method of claim 6 , wherein the secretory signal peptide comprises the rice alpha-amylase secretory signal peptide.
8. The method of claim 1 , wherein the cholera toxin B subunit variant comprises two or more N-linked glycosylation sequons.
9. The method of claim 1 , wherein the cholera toxin B subunit variant comprises an amino acid sequence selected from SEQ ID NO: 4, 5, 8, 10, 12, 14, 25, 26, 27, 28, or 29.
10. The method of claim 1 , wherein the cholera toxin B subunit variant comprises the amino acid sequence of SEQ ID NO: 4.
11. The method of claim 1 , wherein the cholera toxin B subunit variant is substantially immunologically identical to a cholera toxin B subunit.
12. The method of claim 1 , wherein the composition is administered to the subject without significantly changing a fecal microbiome of the subject.
13. The method of claim 1 , wherein the administering of the composition comprises oral administration.
14. The method of claim 1 , wherein the administering of the composition decreases protein levels of tumor promoting cytokines.
15. The method of claim 1 , wherein the method promotes mucosal wound healing in the colon.
16. The method of claim 15 , wherein the C-terminal ER retention sequence comprises a hexapeptide sequence.
17. The method of claim 15 , wherein the C-terminal ER retention sequence comprises SEKDEL (SEQ ID NO: 30), KDEL (SEQ ID NO: 31), or HDEL (SEQ ID NO: 32).
18. The method of claim 15 , wherein the C-terminal ER retention sequence comprises KDEL (SEQ ID NO: 31).
19. The method of claim 15 , wherein the cholera toxin B subunit variant comprises the amino acid sequence of SEQ ID NO: 4.
20. The method of claim 15 , wherein the administering of the composition comprises oral administration.