Method for allowing immune cells infiltration in tumors
AssigneeAlethia Biotherapeutics Inc.
InventorMario FILION
Life of this patent
Estimating the term…
Abstract
The present disclosure generally relates to a method for allowing intra-tumor immune infiltration and/or for treating a subject having cancer. The method of the present disclosure is based on the administration of an anti-clusterin antibody or antigen binding fragment thereof either as a single agent or in combination therapy with docetaxel. Combination therapy, medicament and kits for such use are also provided.
Claims209
A method for allowing infiltration of immune cells in a tumor microenvironment, the method comprising administering to a subject in need thereof an anti-clusterin antibody or an antigen binding fragment thereof.
The method of any one of the preceding claims, wherein the method also comprises a step of administering docetaxel to the subject.
The method of any one of the preceding claims, wherein the method results in modulation of an immune response towards tumor cells.
The method of any one of the preceding claims, wherein the subject has a functional immune system.
A method of treating a subject having cancer, the method comprising administering a combination therapy comprising an anti-clusterin antibody or antigen binding fragment thereof and docetaxel, wherein the subject has a functional immune system.
The method of any of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof comprises a light chain variable region comprising the complementarity determining regions (CDRs) of the light chain variable region set forth in SEQ ID NO:9 and a heavy chain variable region comprising the CDRs of the heavy chain variable region set forth in SEQ ID NO:10.
The method of any of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof comprises a light chain variable region having an amino acid sequence having at least 80% identity with the amino acid sequence set forth in SEQ ID NO:9 and a heavy chain variable region having an amino acid sequence at least 80% identity with the amino acid sequence set forth in SEQ ID NO:10.
The method of any of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof comprises a light chain having an amino acid sequence having at least 80% identity with the amino acid sequence set forth in SEQ ID NO:11 and a heavy chain having an amino acid sequence having at least 80% identity with the amino acid sequence set forth in SEQ ID NO:12.
The method of any of the preceding claims, wherein the antibody or antigen binding fragment thereof is capable of competing with an antibody comprising a light chain variable region having an amino acid sequence set forth in SEQ ID NO:9 and a heavy chain variable region having an amino acid sequence set forth in SEQ ID NO:10 for the binding of clusterin.
The method of any of the preceding claims, wherein the method results in infiltration of immune cells in a primary tumor microenvironment.
The method of any one of the preceding claims, wherein the immune cells comprise plasmocytes.
The method of any one of the preceding claims, wherein the immune cells comprise T cells.
The method of any one of the preceding claims, wherein the immune cells comprise B cells.
The method of any of the preceding claims, wherein the treatment results in necrosis of a tumor.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered once weekly.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered twice weekly.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered once every two weeks.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered once every three weeks.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered once every four weeks.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered at a dose of between approximately 3 mg/kg to approximately 20 mg/kg.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered at a dose of approximately 6 mg/kg.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered at a dose of approximately 9 mg/kg.
The method of any one of the preceding claims, wherein the anti-clusterin antibody or antigen binding fragment thereof is administered at a dose of approximately 12 mg/kg.
The method of any one of the preceding claims, wherein the subject has a carcinoma.
The method of any one of the preceding claims, wherein the carcinoma is metastatic.
The method of any of the preceding claims wherein the subject in need has or is selected for having a tumor characterized as immunologically cold.
The method of any of the preceding claims wherein the subject in need has or is selected for having a tumor characterized as immunologically warm or hot that is non-responsive to immunotherapy.
The method of any one of the preceding claims, wherein the subject has or is selected for having a carcinoma that progressed after a first line immune checkpoint therapy.
The method of any one of the preceding claims, wherein the subject has or is selected for having a carcinoma that has failed prior treatment with a platinum-containing doublet treatment and immune checkpoint therapy.
The method of any one of the preceding claims, wherein the subject has or is selected for having a carcinoma that has failed prior treatment with a platinum-containing doublet treatment and an anti-PD1 or PDL-1 immune checkpoint antibody.
The method of any one of the preceding claims, wherein the subject in need has an endometrial cancer, a breast cancer, a liver cancer, a prostate cancer, a renal cancer, an ovarian cancer, a colorectal cancer, a pancreatic cancer, a lung cancer, a gastric cancer, a head and neck cancer, a thyroid cancer, a cholangiocarcinoma, a mesothelioma or a melanoma.
The method of any one of the preceding claims, wherein the subject in need has a metastatic endometrial cancer, a metastatic breast cancer, a metastatic liver cancer, a metastatic prostate cancer, a metastatic renal cancer, a metastatic ovarian cancer, a metastatic colorectal cancer, a metastatic pancreatic cancer, a metastatic lung cancer, a metastatic gastric cancer, a metastatic head and neck cancer, a metastatic thyroid cancer, a metastatic cholangiocarcinoma, a metastatic mesothelioma or a metastatic melanoma.
The method of any one of the preceding claims, wherein the subject is not immunosuppressed or has not received an immunosuppressive medication within 7 days prior to treatment.
The method of any one of the preceding claims, wherein the subject has not received prior treatment with docetaxel.
The method of any of the preceding claims, wherein the subject is treated for at least two cycles of treatment.
The method of any of the preceding claims, wherein infiltration of immune cells in a tumor microenvironment is confirmed by biopsy.
The method of any of the preceding claims, wherein infiltration of immune cells in a tumor microenvironment is confirmed by imaging.
The method of any of the preceding claims, wherein the treatment results in the tumor being more susceptible to treatment by immunotherapy.
The method of any one of the preceding claims, wherein the treatment comprises administering immunotherapy after one or more cycle of combination therapy.
The method of any one of the preceding claims, wherein the subject does not receive concurrent anti-cancer treatment with than the anti-clusterin antibody or antigen binding fragment thereof and/or docetaxel combination treatment.
The method of any one of the preceding claims, wherein the subject is a human subject.
A combination therapy comprising a pharmaceutical composition comprising an anti-clusterin antibody or antigen binding fragment thereof formulated for administration at a dose of between approximately 3 mg/kg to approximately 20 mg/kg and a pharmaceutical composition comprising docetaxel formulated for administration at a dose of approximately 60 mg/m2 to 100 mg/m2.
A kit comprising one or more containers comprising at least one dose of an anti-clusterin antibody or antigen binding fragment thereof, one or more containers comprising at least one dose of docetaxel for use in combination therapy and a package insert comprising instructions for treating a subject in need.
A medicament comprising an anti-clusterin antibody or antigen binding fragment thereof for allowing infiltration of immune cells in a tumor microenvironment in a subject having cancer.
A medicament comprising an anti-clusterin antibody or antigen binding fragment thereof for use in combination with docetaxel for the treatment of a subject having cancer wherein the subject has a functional immune system.
Use of an anti-clusterin antibody or an antigen binding fragment thereof for allowing infiltration of immune cells in a tumor microenvironment in a subject in need thereof.
Use of an anti-clusterin antibody or an antigen binding fragment thereof in the manufacture of a medicament or kit for allowing infiltration of immune cells in a tumor microenvironment in a subject in need thereof.
Use of a combination therapy comprising an anti-clusterin antibody or antigen binding fragment thereof and docetaxel in the treatment of a subject having cancer, wherein the subject has a functional immune system.
Use of an anti-clusterin antibody or antigen binding fragment thereof and docetaxel in the manufacture of a medicament or kit for the treatment of a subject having cancer, wherein the subject has a functional immune system.
Dependencies are inferred from the claim text.