초록 ▼

An immunogen includes an isolated peptide of 800 amino acid residues or fewer having the amino sequence ILSAFSVYV (SEQ ID NO:1) with four or fewer amino acid substitutions, a superagonist variant of SEQ ID NO:1, or an amino acid sequence having the formula: (I/K/T/V/M)-L-(S/L)-(A/E/N/D/Q)-(F/V)-(S/M

An immunogen includes an isolated peptide of 800 amino acid residues or fewer having the amino sequence ILSAFSVYV (SEQ ID NO:1) with four or fewer amino acid substitutions, a superagonist variant of SEQ ID NO:1, or an amino acid sequence having the formula: (I/K/T/V/M)-L-(S/L)-(A/E/N/D/Q)-(F/V)-(S/M/V/I)-(V/D/R/G/H)-Y-(V/I/L) (SEQ ID NO:13). The immunogens can be used in compositions and in the treatment of disorders.

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1. A method of inducing a cytotoxic T lymphocyte (CTL) response in a human subject, the method comprising administering to the subject an effective amount of a composition comprising an isolated immunogen of 9 to 50 amino acid residues comprising a peptide consisting of the amino sequence set forth

1. A method of inducing a cytotoxic T lymphocyte (CTL) response in a human subject, the method comprising administering to the subject an effective amount of a composition comprising an isolated immunogen of 9 to 50 amino acid residues comprising a peptide consisting of the amino sequence set forth in SEQ ID NO:1 with four or fewer amino acid substitutions within SEQ ID NO:1, wherein the four or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1, wherein the peptide is a CD133 HLA-A2 restricted epitope, and wherein the administration of the composition comprising the isolated immunogen elicits a peptide-specific CTL response to cells expressing HLA-A2 and presenting the peptide. 2. The method of claim 1, wherein the composition further comprises an adjuvant, cytokine, or vehicle. 3. A method of inducing a therapeutic cytotoxic T lymphocyte (CTL) response in a mammalian subject, the method comprising administering to the subject an effective amount of a composition comprising an isolated peptide having the amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, with four or fewer amino acid substitutions within said amino acid sequence, wherein the four or fewer amino acid substitutions do not occur at position 2 or position 8 of said amino acid sequence, wherein the peptide is a CD133 HLA-A2 restricted epitope, and wherein the administration of the composition elicits a peptide-specific CTL response to cancer cells expressing HLA-A2 and presenting the peptide. 4. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:1. 5. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:11. 6. The method of claim 1, wherein the isolated immunogen is 9 to 30 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with four or fewer amino acid substitutions within SEQ ID NO:1, wherein the four or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 7. The method of claim 1, wherein the isolated immunogen is 9 to 30 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with two or fewer amino acid substitutions within SEQ ID NO:1, wherein the two or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 8. The method of claim 1, wherein the isolated immunogen is 9 to 30 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1. 9. The method of claim 1, wherein the isolated immunogen is 9 to 20 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with four or fewer amino acid substitutions within SEQ ID NO:1, wherein the four or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 10. The method of claim 1, wherein the isolated immunogen is 9 to 20 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with two or fewer amino acid substitutions within SEQ ID NO:1, wherein the two or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 11. The method of claim 1, wherein the isolated immunogen is 9 to 20 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1. 12. The method of claim 1, wherein the isolated immunogen is 9 to 15 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with four or fewer amino acid substitutions within SEQ ID NO:1, wherein the four or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 13. The method of claim 1, wherein the isolated immunogen is 9 to 15 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with two or fewer amino acid substitutions within SEQ ID NO:1, wherein the two or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 14. The method of claim 1, wherein the isolated immunogen is 9 to 15 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1. 15. The method of claim 1, wherein the isolated immunogen immunogen is 9 to 12 amino acids length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with four or fewer amino acid substitutions within SEQ ID NO:1, wherein the four or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 16. The method of claim 1, wherein the isolated immunogen is 9 to 12 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1 with two or fewer amino acid substitutions within SEQ ID NO:1, wherein the two or fewer amino acid substitutions do not occur at position 2 or position 8 of SEQ ID NO:1. 17. The method of claim 1, wherein the isolated immunogen is 9 to 12 amino acids in length and comprises a peptide consisting of the amino acid sequence set forth in SEQ ID NO:1. 18. The method of claim 2, wherein the composition comprises an adjuvant. 19. The method of claim 18, wherein the adjuvant is selected from the group consisting of Toll-like receptor agonists, Bacillus Calmette Guerin, complete or incomplete Freund's adjuvant, a cytosine guanine oligodeoxynucleotide, Montanide ISA-51, Activation Gene-3, aluminum phosphate, aluminum hydroxide, alum, and saponin. 20. The method of claim 2, wherein the composition comprises a cytokine. 21. The method of claim 20, wherein the cytokine is selected from the group consisting of Interleukin-1, Interleukin-2, Interleukin-7, Interleukin-12, Interleukin-13, Interleukin-15, tumor necrosis factor, stem cell factor, and granulocyte monocyte colony stimulating factor. 22. The method of claim 3, wherein the composition further comprises an adjuvant, cytokine, or vehicle. 23. The method of claim 1, wherein the four or fewer amino acid substitutions within SEQ ID NO:1 are conservative amino acid substitutions. 24. The method of claim 1, wherein the immunogen comprises a peptide consisting of the amino sequence set forth in SEQ ID NO:1. 25. A method for inducing a cytotoxic T lymphocyte (CTL) dependent immune response in a human subject, the method comprising: (a) isolating CTLs and autologous dendritic cells (DCs) from the subject;(b) contacting the CTLs ex vivo with autologous DCs pulsed with a peptide, thereby creating peptide-specific CTLs, wherein the peptide consists of the amino sequence set forth in SEQ ID NO:1 with four or fewer acid substitutions within SEQ ID NO:1;(c) administering to the subject an effective amount of the peptide-specific CTLs, wherein the peptide-specific CTLs recognize both HLA-A2 and CD133 positive cancer stem cells, thereby eliciting a CD133-specific-CTL response. 26. The method of claim 25, wherein the peptide consists of the sequence set forth in SEQ ID NO:1. 27. The method of claim 25, wherein the subject has cancer. 28. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:6. 29. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:7. 30. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:8. 31. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:9. 32. The method of claim 3, wherein the peptide consists of the sequence set forth in SEQ ID NO:10.