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AssigneesNational University Corporation Okayama University, Ono Pharmaceutical Co., Ltd.
InventorsHeiichiro UDONO, Shingo EIKAWA, Shin-ichi TOYOOKA
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The invention provides a method for enhancing immune cell function by activating various immune cells ex vivo and provides immune cells with enhanced function. The invention further provides an immune-related cell multifunctionality evaluation method. A biguanide antidiabetic drug selected from metformin, phenformin, and buformin is capable of enhancing immune cell multifunctionality by increasing CD8+T cells having a high ability to produce IL-2, INFα, and IFNγ. The immune-related cell multifunctionality may be evaluated by comparing immune cells treated with a biguanide antidiabetic drug selected from metformin, phenformin, and buformin, with control immune cells untreated with the biguanide antidiabetic drug. When the multifunctionality of immune cells treated with the biguanide antidiabetic drug selected from metformin, phenformin, and buformin is determined to be significantly increased compared with the control, it can be evaluated that the sensitivity of the immune cells to the therapeutic agent is improved.
A method of treating and/or preventing a disease associated with an immune abnormality in a patient, comprising administering (a) a biguanide antidiabetic drug selected from metformin, phenformin, and buformin and (b) at least one therapeutic agent selected from immunosuppressive factor blocking agent and costimulatory receptor agonist to the patient to treat and/or prevent a disease associated with an immune abnormality in the patient.
A method of treating and/or preventing recurrence of cancer in a patient, comprising administering (a) metformin and (b) an anti-PD-1 antibody to the patient to treat and/or preventing recurrence of cancer in the patient, wherein the cancer is at least one cancer selected from head and neck cancers, esophagus cancer, gastric cancer, colorectal cancer, hepatocellular cancer, pancreatic cancer, non-small cell lung cancer, small cell lung cancer, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, vaginal cancer, vulvar cancer, renal cell cancer, urothelial cancer, Hodgkin's lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, multiple myeloma, malignant melanoma, glioblastoma and pleural mesothelioma.
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