Abstract: A combination of retinoic acid, an anti-O-acetylated disialoganglioside (OAcGD2) compound and an anti-PD1/PD-L1 compound for treating a cancer, particularly neuroblastoma, in a subject in need thereof. The inventors focused on immunotherapeutic strategies targeting OAcGD2, believing they could address critical neuropathic pain side effects associated with anti-GD2 mAb infusions. They reported mAb 8B6 targeting OAcGD2 displays antitumor activity in NB tumor models, with induction of ADCC similarly to anti-GD2 mAbs. From this, the inventors interrogated whether 13-cis-RA and retinoic acid generally, may augment anti-NB efficiency of mAb 8B6 therapy. They found cooperative interaction of 13-cis-RA and mAb 8B6 treatment in inhibiting the NB growth in vivo. However, this combination regimen also coordinates PD-1/PD-L1 upregulation, which hinders a long-term activation of NK cells and allows tumor cell to relapse.

Abstract: The treatment of cancer and particularly the neuroblastoma, and a combination of an anti-O-acetylated disialoganglioside (OAcGD2) compound and an anti-SIRP-alpha/CD47 compound for treating a cancer in a subject in need thereof. The inventors hypothesized that CD47 expression would interfere with the contribution of macrophage to the therapeutic effect of anti-OAcGD2 mAbs. They found that NB cells up-regulate CD47 expression upon 8B6 mAb immunotherapy in vivo, allowing them to escape mAb 8B6-mediated ADP. Next, they demonstrate that an anti-SIRP? antibody that blocks the binding of CD47 to SIRP? enables macrophages to phagocyte anti-OAcGD2-opsonised CD47-expressing NB cells in vitro. As a result, the combination of CD47 blocking with the targeting of OAcGD2-positive NB cells greatly reduces tumor growth in syngeneic mice.

Abstract: The use of CASD1 as a biomarker of a cancer expressing the O-acetylated-GD2 ganglioside. Also, a method of diagnosing a cancer expressing the O-acetylated-GD2 ganglioside, a method of selecting a subject suffering from a cancer expressing the O-acetylated-GD2 ganglioside for treatment targeting the cancer, or a method of monitoring the response of a subject suffering from a cancer expressing the O-acetylated-GD2 ganglioside to a treatment targeting the cancer.

Abstract: Disclosed is a method for delivery of an anti-cancer agent into a cell expressing the OAcGD2 ganglioside by using an antibody recognizing the OAcGD2 ganglioside.

Abstract: Disclosed is an antibody, functional fragment, and derivative thereof, which binds specifically to the OAcGD2 ganglioside, the antibody including i) a humanized light chain variable region (VL) polypeptide having the amino acid sequence SEQ id no 112; and ii) a humanized heavy chain variable region (VH) having the amino acid sequence SEQ id no 76; and its use in diagnostics and therapy.

Abstract: 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.

Abstract: A method for increasing the therapeutic efficacy of a human immunoglobulin G class 1 (IgG1) antibody, includes: mutating the human CH1?1 domain from the antibody, to restore the pairing between CH1 and CL domains that is typical of the other IgG subclasses, or by substituting the human CH1?1 domain by the CH1 domain from a human IgG2 (CH1?2), IgG3 (CH1?3) or IgG4 (CH1?4); the antibody obtained by such method, includes a) a light chain including the following amino acid sequences: i) the Light Chain Variable Region (LCVR) specific from an antigen; and ii) a human kappa (?)Constant (CL) domain; and b) a heavy chain including the following amino acid sequences: i) the Heavy Chain Variable Region (HCVR) specific from the antigen; ii) the CH2 and CH3 domains from a human IgG1; and iii) the CH1 domain from a human IgG1, mutated to restore pairing between CHI and CL domains.

Abstract: Antibody which binds to the O-acetylated-GD2 ganglioside, includes: a) a light chain including three light chain complementary regions (CDRs) having the following amino acid sequences: CDR1: QSLLKNNGNTFL (SEQ id no 1), CDR2: KVS, CDR3: SQSTHIPYT (SEQ id no 2); and a light chain framework sequence from an immunoglobulin light chain, including the human kappa (?)CL domain; and b) a heavy chain including three heavy chain complementary regions (CDRs) having the following amino acid sequences: CDR1: EFTFTDYY (SEQ id no 3), CDR2: IRNRANGYTT (SEQ id no 4), CDR3: ARVSNWAFDY (SEQ id no 5), and a heavy chain framework sequence from an immunoglobulin heavy chain, including CH2 and CH3 domains from a human IgG1, and a CH1 domain from a human IgG1, which is mutated to restore pairing between CH1 and light chain that is typical of other human IgG subclasses or substituted by a CH1 domain from such non-IgG1 subclasses as human IgG2, IgG3 or IgG4.

Abstract: Disclosed is an antibody, functional fragment, and derivative thereof, which binds specifically to the OAcGD2 ganglioside, the antibody including i) a humanized light chain variable region (VL) polypeptide having the amino acid sequence SEQ id no 112; and ii) a humanized heavy chain variable region (VH) having the amino acid sequence SEQ id no 76; and its use in diagnostics and therapy.

Abstract: 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.