Modulators of MYC, methods of using the same, and methods of identifying agents that modulate MYC
View Patent ↗Disclosed herein are methods of modulation of the viability of a cell. Further disclosed herein are methods of modulating an immune response. Further disclosed herein are methods of identifying agents capable of modulation of the viability of a cell or an immune response. Further disclosed herein are agents and compositions capable of modulation of the viability of a cell or an immune response.
1. A method, comprising:
(a) providing an antigenic moiety and a fusion peptide to one or more immune cells in vitro, wherein the fusion peptide comprises:
(i) a transporter peptide sequence;
(ii) a MYC polypeptide sequence; and, optionally,
(iii) one or more molecules that link the transporter peptide sequence and the MYC polypeptide sequence; and
(b) culturing the one or more immune cells under conditions sufficient for the fusion peptide to increase one or more of activation, survival, or proliferation of the one or more immune cells, as compared with corresponding immune cells not exposed to the fusion peptide.
2. The method of claim 1 , wherein increasing activation comprises one or more of decreasing the amount of time it takes for the one or more immune cells to respond to an antigenic moiety or increasing the rate or amount the one or more immune cells proliferate in response to an antigenic moiety.
3. The method of claim 1 , wherein increasing proliferation comprises increasing the rate or amount the one or more immune cells proliferate.
4. The method of claim 1 , wherein increasing survival comprises increasing the length of time the one or more immune cells survive.
5. The method of claim 1 , wherein the one or more immune cells comprise T cells.
6. The method of claim 1 , wherein the one or more immune cells comprise B cells.
7. The method of claim 1 , wherein the one or more immune cells are one or more factor-dependent, antigen-activated immune cells; and wherein the culturing of the one or more factor-dependent, antigen-activated immune cells is in the absence of a cytokine.
8. The method of claim 1 , wherein the one or more immune cells are one or more activated immune cells.
9. The method of claim 1 , wherein the fusion peptide has Formula (I):
transporter peptide sequence-MYC polypeptide sequence.
10. The method of claim 1 , wherein the fusion peptide has Formula (II):
transporter peptide sequence-X-MYC polypeptide sequence,
wherein —X— is the one or more molecules that link the transporter peptide sequence and the MYC polypeptide sequence.
11. The method of claim 1 , wherein the fusion peptide has Formula (II):
transporter peptide sequence-X-MYC sequence,
wherein in —X— is at least one amino acid that links the transporter peptide sequence and the MYC polypeptide sequence.
12. The method of claim 1 , wherein the fusion peptide has the following sequence (SEQ ID NO: 2):
MRKKRRQRRRMDFFRVVENQQPPATMPLNVSFTNRNYDLDYDSVQPYF
YCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPTPPLSPSRRSGLCS
PSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGGDMVNQSFICDP
DDETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPARG
HSVCSTSSLYLQDLSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSA
FSPSSDSLLSSTESSPQGSPEPLVLHEETPPTTSSDSEEEQEDEEEID
VVSVEKRQAPGKRSESGSPSAGGHSKPPHSPLVLKRCHVSTHQHNYAA
PPSTRKDYPAAKRVKLDSVRVLRQISNNRKCTSPRSSDTEENVKRRTH
NVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSVQ
AEEQKLISEEDLLRKRREQLKHKLEQLRKGELNSKLEGKPIPNPLLGL
DSTRTGHHHHHH.
13. The method of claim 1 , wherein the antigenic moiety is a peptide, a nucleic acid sequence, or a polysaccharide; derived from a neoplastic cell, a pathogen, or a toxoid; or a combination thereof.
14. The method of claim 1 , wherein the antigenic moiety is derived from a pathogen selected from the group consisting of hepatitis A; hepatitis B; polio; measles; mumps; rubella; diphtheria; pertussis; tetanus; influenza; varicella zoster virus; rotavirus; meningococcal; pneumonia; smallpox; cholera; bubonic plague; yellow fever; tuberculosis; human papillomavirus; and combinations thereof.