ANTIBODY TOOLS FOR THE DIAGNOSTIC USE IN THE MEDICAL THERAPY WITH INHIBITORS OF HISTONE DEACETYLASES

摘要

Determining (M1) whether treatment of disorder with histone deacetylase (HDAC) inhibitor is to be started/continued/not by contacting sample from tissue affected by disorder with antibody binding to acetylated histone but not to deacetylated histone, determining histone level acetylation in sample and classifying disorder as to be treated with HDAC inhibitor when histone acetylation level is significantly less than control sample. Independent claims are also included for: (1) use of an antibody capable of binding to acetylated histone for determining whether a treatment of a disorder with an HDAC inhibitor is to be started/continued or not, and/or the classification of tumors; (2) an antibody (I) capable of binding to peptides having a sequence of Ser-Gly-Arg-Gly-Lys-Gly-Gly-Lys-Gly-Leu-Gly-Lys-Gly-Gly-Ala-Lys- Arg (histone H4 tail, mono-acetylated at lysine 8) (S1) and Ser-Gly-Arg-Gly-Lys-Gly-Gly-Lys-Gly-Leu-Gly-Lys-Gly-Gly-Ala-Lys- Arg (histone H4 tail, mono-acetylated at lysine 12) (S2) but not to anyone of the peptides having the sequences of Ser-Gly-Arg-Gly-Lys-Gly-Gly-Lys-Gly-Leu-Gly-Lys-Gly-Gly-Ala-Lys- Arg (histone H4 tail, mono-acetylated at lysine 16) (S3), Ser-Gly-Arg-Gly-Lys-Gly-Gly-Lys-Gly-Leu-Gly-Lys-Gly-Gly-Ala-Lys- Arg (non-acetylated peptide) (S4), Ala-Val-Cys-Asp-Lys-Cys-Leu-Lys-Phe-Tyr-Ser-Lys and Val-Trp-Asp-Gln-Glu-Phe-Leu-Lys-Val-Asp-Gln-Gly; (3) an antibody (II) capable of binding to peptides having (S1), (S2) and (S3) but not to peptides having (S4); (4) an antibody produced by a hybridoma cell line chosen from hybridoma cell lines G2M-T25-H4ac and G2M-T52-ac deposited at DSMZ; (5) a hybridoma cell line producing (I) or (II); (6) a hybridoma cell line which has the identifying characteristics of the cell line G2M-T25-H4ac deposited at DSMZ; (7) a hybridoma cell line which has the identifying characteristics of the cell line G2M-T52-ac deposited at DSMZ; (8) a diagnostic kit (III) for determining the level of histone acetylation containing an antibody capable of binding to acetylated histone but not to deacetylated histone, an HDAC inhibitor, and optionally, a secondary antibody directed against the antibody, and optionally reagents for the measurement of a signal derived from an antibody binding to acetylated histones; and (9) use of the antibodies T25 and/or T52 (IV) to direct substances conjugated to these antibodies to sites of histone hyperacetylation.