Targeting O-acetylated GD2 ganglioside as a new therapeutic and diagnostic strategy for cancer stem cells cancer
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 treating a cancer stem cell (CSC) cancer comprising cells having at least one phenotype selected from the group consisting of:
Cancer type
CSC biomarkers and/or phenotypes
Acute myeloid
CD34 + /CD38 −
leukemia
interleukin-3-receptor α +
CD33 +
Acute lymphoid
CD34 + /CD19 +
leukemia
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 +
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 +
the method comprising administering to a subject in need thereof an effective amount of an antibody recognizing the O-acetylated-GD2 ganglioside, or a functional fragment of said antibody, wherein said antibody comprises:
a) a light chain comprising at least a light chain variable region framework from an immunoglobulin and three complementary determining regions (CDRs), the CDRs defined by the sequences SEQ ID NO: 1 for CDR-L1, SEQ ID NO: 2 for CDR-L2, and SEQ ID NO: 3 for CDR-L3, and
b) a heavy chain comprising at least a heavy chain variable region framework from an immunoglobulin and three complementary determining regions (CDRs), the CDRs defined by the sequences SEQ ID NO: 4 for CDR-H1, SEQ ID NO: 5 for CDR-H2, and SEQ ID NO: 6 for CDR-H3,
and wherein the treatment is based upon elimination of said cancer stem cells.
2. The method of claim 1 , wherein said functional fragment of said antibody is selected from the group consisting of Fab, Fab′, F(ab′) 2 , Facb, scFv, and diabodies.
3. The method of claim 1 , wherein said antibody is a chimeric or a humanized antibody.
4. The method of claim 1 , wherein said antibody comprises a light chain variable region comprising the amino acid sequence SEQ ID NO: 7 and a heavy chain variable region comprising the amino acid sequence SEQ ID NO: 8.
5. The method of claim 1 , wherein said CSC cancer is selected the group consisting of leukemia, acute myeloid leukemia, acute lymphoid leukemia, breast cancer, glioma, glioblastoma, pancreatic cancer, prostate cancer, lung cancer, liver cancer, bladder cancer and gastric cancer.
6. The method of claim 1 , wherein said CSC cancer comprises cells having at least a CD133 + , CD44 + /CD24 −/low , CD34 + /CD38 − or CD34 + /CD19 + phenotype.
7. The method of claim 1 , wherein said CSC cancer is breast cancer, glioma, acute myeloid leukemia or acute lymphoid leukemia.
8. The method of claim 1 , wherein said CSC cancer is characterized by a subpopulation of cancer stem cells in which at least 10% of cancer stem cells express the O-acetylated-GD2 ganglioside.
9. The method of claim 1 , wherein said antibody is for treating metastasis or metastases of a CSC cancer and/or for preventing relapse or recurrence of a CSC cancer.
10. The method of claim 1 , wherein the method further comprises separate, simultaneous or sequential administration of at least one other anti-cancer compound to the subject.
11. The method of claim 1 , wherein the administered antibody or functional fragment thereof is separately, simultaneously or sequentially combined with surgery, chemotherapy, hormonal therapy, targeted therapy and/or radiotherapy.