ROLE OF ANTI-CCR4 HUMANIZED MONOCLONAL ANTIBODIES IN CUTANEOUS T-CELL LYMPHOMA AND OTHER CANCERS
Cutaneous T-cell Lymphomas and other cancers
The antibody can be used to treat, prevent or alleviate symptoms of Cutaneous T-cell lymphomas as well as solid tumors such as s breast cancer, lung cancer, ovarian cancer, prostate cancer, colon cancer, cervical cancer, brain cancer, liver cancer, pancreatic cancer or stomach cancer. It can be used in combination with vaccines to suppress the activity of regulatory T cells and augment the response of effector T-cells.
Humanized monoclonal antibody that binds to the chemokine receptor, CCR4, was developed from a murine anti-CCR4 monoclonal antibody (mAb), mAb1567. The chemokine receptor, CCR4, is uniformly expressed in Cutaneous T-cell lymphomas (CTCL) cells but is either absent on naϊve T cells or present on fewer than half of all memory T cells. This makes targeted therapy of CCR4 an attractive goal for CTCL, thereby minimizing collateral damage to an already compromised immune system. While some progress has been made in identifying small molecule inhibitors that are relatively selective for CCR4, specific monoclonal antibodies against CCR4 are an attractive candidate for immunotherapy of CTCL because of their exquisite binding specificity. The therapeutic anti-CCR4 monoclonal antibody not only directly kills the CCR4+ tumor cells, but also helps to overcome the immunosuppressive effect of CCR4+ regulatory T cells, which are attracted to the tumor by the chemokines and specific CCR4 ligands to create a microenvironment to escape the host immune responses. The invention also encompasses kits for detecting the presence of CCR4 or a CCR4-expressing cell in a biological sample.
Inventor: MARASCO, Wayne, A. | SUI, Jianhua | ZHU, Quan | KUPPER, Thomas
Priority Number: WO2009086514A1
IPC Current: C07K001628 | A61K0039395 | C07K001630
Assignee Applicant: Dana-Farber Cancer Institute Inc. | The Brigham & Women's Hospital Inc.
Title: HUMANIZED MONOCLONAL ANTIBODIES AND METHODS OF USE | ANTICORPS MONOCLONAUX HUMANISÉS ET PROCÉDÉS D'UTILISATION
Usefulness: HUMANIZED MONOCLONAL ANTIBODIES AND METHODS OF USE | ANTICORPS MONOCLONAUX HUMANISÉS ET PROCÉDÉS D'UTILISATION
Summary: The isolated humanized monoclonal CC-chemokine receptor 4 (CCR4) antibody or its fragment is useful for selectively killing a tumor cell, decreasing suppressor T-cell activity, augmenting immune response to antigen such as viral antigen such as HIV, bacterial antigen or tumor associated antigen, and increasing efficiency of vaccine e.g. tumor vaccine, bacterial vaccine or viral vaccine for preventing and/or treating cancer such as solid cancer or hematologic cancer e.g. cutaneous T-cell Lymphoma (CTCL), mycosis fungoides (MF), primary cutaneous anaplastic large cell lymphoma (cutaneous ALCL), sezary syndrome, or adult T cell leukemia/lymphoma (ATLL). The solid cancer is such as breast cancer, lung cancer, ovarian cancer, prostate cancer, colon cancer, cervical cancer, brain cancer, liver cancer, pancreatic cancer, kidney cancer or stomach cancer (all claimed).
Novelty: Novel humanized monoclonal CC-chemokine receptor (CCR)4 antibody capable of binding to CCR4 positive cells, useful for improving immune response to antigen, and increasing vaccine efficiency for treating cancer, e.g. lung cancer
Disease Diagnostic/Treatment
HIV
USA
