CD4+ T epitoper af survivin og deres anvendelse

摘要

Peptides (P) derived from the alpha -isoform of survivin (Sa) for use as antigen in prophylactic or therapeutic vaccination; and for diagnosis, prognosis or therapeutic monitoring of cancer. (P) comprise (a) 13-18 consecutive amino acids (aa) between positions 17 and 34 of Sa; (b) 13-30 consecutive aa between positions 84 and 113; (c) 13-21 aa between positions 122 and 142, or (d) variants of (a)-(c). All P have binding activity, to at least one HLA-II molecule preponderant in Caucasians, of below 1000 nM and can induce CD4 +> T lymphocytes specific for survivin. Independent claims are included for the following: (1) polyepitopic fragment (X) comprising the concatenation of at least two epitopes, same or different, at least one being a P, for use as antigen as above; (2) fusion protein (FP) containing a protein (or fragment) fused to P or X, for use as antigen as above; (3) lipopeptide (LP) obtained by adding a lipid to the alpha -amino or reactive sidechains of P or X, for use as antigen as above; (4) expression vector that contains a polynucleotide encoding P, X or LP, under control of appropriate regulators, for use as antigen as above; (5) immunogenic or vaccinating composition containing at least one P, X, FP, LP, vector of (4) plus vehicle, carrier or adjuvant; (6) method for diagnosis, prognosis or monitoring of cancer by contacting, in vitro, a patient sample with P and detecting CD4 +> T cells specific for survivin; (7) method for selecting CD4 +> T cells specific for survivin by contacting, in vitro, a cell sample with labeled multimeric complex formed between HLA-II molecule and at least one P, then isolating cells that have bound the complex; (8) P as new compounds, except for the peptide containing aa 89-101 of alpha -survivin; (9) (X), FP and LP as new compounds; (10) new polynucleotides that encode P, X and FP; (11) the vector of (4) as new; and (12) host cells modified by the nucleic acid/vectors of (11) and (12). ACTIVITY : Cytostatic. No details of tests for cytostatic activity are given. MECHANISM OF ACTION : Vaccine. Survivin is an apoptosis inhibitor, overexpressed in most tumors, and if its expression is prevented, human cancer cell lines are prevented from dividing and undergo apoptosis. Survivin mRNA is also a good prognostic indicator; high levels being associated with a poor prognosis. The new process induces a tumor-specific CD4 +>/CD8 +> T cell response.