Targeting o-acetylated gd2 ganglioside as a new therapeutic and diagnostic strategy for
An antibody recognizing the O-acetylated-GD2 ganglioside for the treatment of Cancer Stem Cells (CSC) cancer, a pharmaceutical composition including the antibody for treating a CSC cancer and a method for treating a CSC cancer in a patient in need thereof, the method including administering the antibody to the patient. A method for diagnosing a CSC, the use of the O-acetylated-GD2 ganglioside as a biomarker of CSC cancer, and a method for predicting the response of a subject affected with CSC cancer to a treatment with the antibody or the composition are also described.
1. A method of detecting O-acetylated-GD2 ganglioside (OAcGD2) in a subject suspected of having a cancer stem cell (CSC) cancer, comprising:
i) obtaining a biological sample comprising tumor cells from said subject;
ii) detecting whether OAcGD2 is coexpressed with at least one CSC biomarker selected from the group consisting of:
Cancer type
CSC biomarkers and/or phenotypes
Acute myeloid leukemia
CD34 + /CD38 −
interleukin-3-receptor α +
CD33 +
Acute lymphoid leukemia
CD34 + /CD19 +
CD34 + /CD19 −
CD34 + /CD38 + /CD19 +
CD34 + /CD38 − /CD19 +
interleukin-3-receptor α +
CD33 +
CD133 + /CD38 −
CD133 + /CD19 −
Breast cancer
CD44 + /CD24 −/low
CD44 + /CD24 −/low /ESA +
CD44 + /CD24 −/low /lin − /ALDH1 +
Glioma cancer
CD133 +
A2B5 +
SSEA-1 +
Colorectal cancer
CD133 + /ESA high /CD44 +
CD166 +
CD26 +
Pancreatic cancer
CD133 +
CD44 + /CD24 + /ESA +
Prostate cancer
CD44 + /CD133 + /α2β1 +
CD44 +
Lung cancer
Sca + /CD45 − /Pecam − /CD34 +
ALDH1 + /Oct4 + /CD133 + /ABCG2 + /CXCR4 +
Liver cancer
CD133 + /CD44 +
EpCAM + /AFP +
Bladder cancer s
EMA − /CD44v6 +
Gastric cancer
CD133 + /CD44 +
CD44 + , CD133 + /CD44 + /ALDH1 +
at the surface of CSC by contacting the biological sample with an anti-OAcGD2 antibody and with at least one antibody specific for the at least one CSC biomarker and detecting binding between OAcGD2 and the corresponding antibody and between the at least one CSC biomarker and the corresponding antibody, wherein the anti-OAcGD2 antibody comprises a heavy chain variable region comprising SEQ ID NO:7 and a light chain variable region comprising SEQ ID NO:8.
2. The method of claim 1 , wherein the anti-OAcGD2 antibody bind the O-acetylated-GD2 ganglioside with an affinity of less than 10 −7 M.
3. The method of claim 1 , wherein the anti-OAcGD2 antibody is labelled with a fluorophore, chromophore, radioelement, enzyme or conjugated with a substrate or with the protein or ligand of a protein of a protein/ligand pair.
4. The method of claim 1 , wherein the detecting is by a method based on enzyme immunoassay (EIA), radioimmunoassay (RIA), Western blot analysis, enzyme linked immunoabsorbant assay (ELISA), Immuno Thin Layer Chromatography (ITLC), flow cytometry or FACS.
5. The method of claim 1 , wherein at least 10% of cancer stem cells (CSC) express the O-acetylated-GD2 ganglioside.
6. The method of claim 1 , wherein CSC have at least one phenotype selected from the group consisting of: OAcGD2 + /CD34 + /CD38 − , OAcGD2 + /CD34 + / CD19 − , OAcGD2 + /CD34 + /CD19 + , OAcGD2 + /CD34 + /CD38 + /CD19 + , OAcGD2 + /CD34 + /CD38 − /CD19 + , OAcGD2 + /CD133 + /CD38 − , OAcGD2 + /CD133 + /CD19 − , OAcGD2 + /interleukin-3-receptor α + , OAcGD2 + / CD 33 + , OAcGD2 + / CD 44 + /CD24 −/ low , OAcGD2 + /CD44 + /CD24 −/low /ESA + , OAcGD2 + /CD44 + /CD24 −/low /lin − /ALDH1 + , OAcGD2 + /CD133 + , OAcGD2 + /A2B5 + , OAcGD2 + /SSEA-1 + , OAcGD2 + /CD133 + /ESA high /CD44 + , OAcGD2 + /CD166 + , OAcGD2 + /CD26 + , OAcGD2 + /CD44 + /CD133 + /α2β1 + , OAcGD2 + /CD44 + , OAcGD2 + /Sca + /CD45 − /Pecam − /CD34 + , OAcGD2 + /ALDH1 + /Oct4 + /CD133 + /ABCG2 + /CXCR4 + , OAcGD2 + /CD133 + /CD44 + , OAcGD2 + /EpCAM + /AFP + , OAcGD2 + /EMA − /CD44v6 + , and OAcGD2 + /CD133 + /CD44 + /ALDH1 +.
7. The method of claim 6 , wherein CSC have the phenotype OAcGD2 + /CD44 + /CD24 −/low , OAcGD2 + /CD44 + /CD24 −/low /ESA + , or OAcGD2 + /CD44 + /CD24 −/low /lin − /ALDH1 +.
8. The method according to claim 1 ; wherein the biological sample is obtained from a solid tumor or a blood sample.
9. The method of claim 1 , wherein the anti-OAcGD2 antibody binds the O-acetylated-GD2 ganglioside with an affinity of less than 5×10 −8 M.
10. The method of claim 1 , wherein the anti-OAcGD2 antibody binds the O-acetylated-GD2 ganglioside with an affinity of less than 10 −8 M.
11. The method of claim 1 , wherein at least 30% of cancer stem cells (CSC) express the O-acetylated-GD2 ganglioside.
12. The method of claim 1 , wherein at least 50% of cancer stem cells (CSC) express the O-acetylated-GD2 ganglioside.