Cysteine-depleted peptides recognized by A3-restricted cytotoxic lymphocytes, and uses therefor

• US 6,558,671 B1
• Filed: 09/20/1999
• Issued: 05/06/2003
• Est. Priority Date: 01/30/1997
• Status: Expired due to Term

• Current Assignee: Rhearg, LLC
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Slingluff, Craig L., Kittlesen, David, Engelhard, Victor H., Hunt, Donald F.
• Primary Examiner(s): Housel, James
• Assistant Examiner(s): JENKS, ULRIKE WINKLER
• Application Number:
  US09/341,982
• Time in Patent Office: 1,324 Days
• Field of Search: 424/185.1, 424/193.1, 424/184.1, 435/7.1, 435/7.24, 435/173.4, 435/173.7, 530/300, 530/326, 530/328, 530/403, 530/327
• US Class Current: 424/185.1
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C12N 2799/023 where the vector is derived from a poxvirus

Abstract

Cysteine-depleted CTL epitopes can elicit a stronger or more specific CTL response than the native, cysteine-containing CTL epitope of a disease associated antigen.

Claims

1. An immunogen which comprises a non-naturally occurring, cysteine-depleted CTL epitope which is a cysteine-depleted mutant of a naturally occurring CTL epitope, and which epitope elicits a greater CTL response than said naturally occurring epitope, differing from said naturally occurring epitope in that at least one cysteine residue of the naturally occurring epitope is replaced with a non-cysteine residue, and where said mutant epitope is otherwise either (a) identical to said naturally occurring epitope or (b) differs therefrom solely by (i) a single conservative substitution, and/or (ii) a single non-conservative substitution, wherein at least one of said cysteine-depleted epitopes is an A1-restricted epitope.

2. The immunogen of claim 1, which is an isolated, purified, or synthetic peptide of about 9 to about 15 residues in length.

3. The immunogen of claim 2 which is tumor-specific.

4. The immunogen of claim 2 wherein said naturally occurring epitope is SEQ ID NO:

19, SEQ ID NO;

37, or SEQ ID NO;

10.

5. The immunogen of claim 2 wherein at least one cysteine of the naturally occurring epitope is replaced by Ala, Thr, Ser, Gly or Met.

6. A composition comprising a peptide according to claim 2 and a class I MHC molecule, whereby T lymphocytes may be stimulated by said peptide.

7. The immunogen of claim 2 in which the native epitope has two cysteines and both are replaced.

8. The immunogen of claim 2 in which the native epitope has two cysteines and only one is replaced.

9. The immunogen of claim 2 in which the native epitope has at least two cysteines.

10. The immunogen of claim 2 in which a Cys at position 2 of the native epitope is replaced.

11. The immunogen of claim 2 in which said mutant epitope is, save for such cysteine replacement, either identical to said naturally occurring epitope or different therefrom solely by a single conservative substitution.

12. the immunogen of claim 2 in which said mutant epitope is, save for such cysteine replacement, identical to said naturally occurring epitope.