ANTIGEN-BINDING PROTEIN RECOGNIZING MAGE-A4-DERIVED PEPTIDE
|Posted date||May 7, 2019|
|International application number||2018JP021561|
|International publication number||WO 2018225732|
|Date of international filing||Jun 5, 2018|
|Date of international publication||Dec 13, 2018|
|Title||ANTIGEN-BINDING PROTEIN RECOGNIZING MAGE-A4-DERIVED PEPTIDE|
[Problem] To provide CAR T cells that can be used in CAR infusion therapy in which a cancer-specific intracellular antigen is used.
[Solution] The problem is solved by CAR T cells for cancer therapy provided with an antibody that recognizes a MAGE-A4-derived peptide and an HLA-A2 complex, wherein the antibody has a VH amino acid sequence of SEQ ID NO: 36 and a VL amino acid sequence of SEQ ID NO: 38. In this case, the antibody preferably is provided with an amino acid sequence of SEQ ID NO: 32.
|Outline of related art and contending technology||
Current, malignant tumor is greater than 30% cause of death, cause of death in developed countries in the first position. Medical advances also the presence of cancer cure, there are many cancers are difficult to treat. Make the new cancer therapy development, a problem of an emergency. As a method of treating cancer, surgery, chemotherapy, radiation therapy and treatment of the three major, or a combination thereof as the main treatment is performed. In recent years, cancer immunotherapy treatment is referred to as the development of the fourth, non-invasive and the height of the effect has attracted attention. Immunotherapy, vaccine therapy mainly, antibody therapy, cells are classified into 3 of the infusion therapy. Cell transfusion therapy is, in response to a cancer-specific cytotoxic T cell-derived T cell receptor gene (T cell receptor: TCR) was introduced at the outside of the lymphocytes of patients after T-cell receptor gene to the infusion therapy diaphramatic lymphocytes, and antigen recognition site of the intracellular signaling molecules as scFv CD3 ζ as chimeric (chimeric antigen receptor antigen receptor bound: CAR) is introduced into the patient's peripheral blood lymphocytes is to treat the infusion. These treatments, antigen-specific lymphocyte receptor gene which has a method for producing a large number in a short time by a variety of cancer can be specific to the patient and the treatment T cells.
TCR gene therapy infusion, peptide MHC complexes (peptide-MHC complex: pMHC) to kill a cancer to recognize since the system, safe and effective treatment and, is currently under development in the world. However, it is the killer T cell clones can be used to isolate a problem that it is very difficult. On the other hand, the advantages of the CAR transfusion therapy and the next 3 points. (1) A single chain antibody (scFv) T cell receptor (TCR) and co-stimulatory molecules and signaling domain CAR T cells are introduced, different from the original T cells, cancer antigen-MHC-independent can be destroyed, and can be adapted to a wide range of patient has an advantage of T cells, (2) as well as CD8 positive, CD4 positive T cells or T cells can be applied also to the non inherits, (3) antibody reactivity for comparison with the TCR, a high affinity. Indeed, CAR therapy, anti-CD19 antibody was used as a therapy to a patient of leukemia and lymphoma CAR extremely high clinical efficacy has been reported (Non-Patent Document 1: for the document, are shown at the end). CD19 Molecule is expressed on the cell B, cell loss B supplemented immunoglobulin can be addressed. In general, to use antigen expressed only in cancer cells is ideal. However, such cell surface antigens, there is a problem that the current is not missing.
On the other hand, the molecules existing within the cell, cancer and testis antigen, such as a specific cancer neoantigen is reported. However, a specific cancer antigen cells will be used in transfusion therapy CAR, has not been known. In view of such circumstances, inventors of the present invention, peptide antigens and MHC complex intracellular antibodies that recognize isolated, using antibodies, immune therapy CAR considered practical applications. Peptide MHC specific antibodies that recognize complex, only a limited number of successful has been reported (Non-Patent Document 2) does not. Peptide MHC complexes to obtain antibodies that specifically recognize specific, specific kill the cancer cells can be made to a CAR-T cells if, for the treatment can be remarkably made. Peptide MHC complexes CAR is recognized, the CAR-T cells within CAR-T cells and at the same time the infusion to specifically recognize peptides can be administered, CAR-T cell proliferation antigen presenting cells can be expected.
|Scope of claims||
|IPC(International Patent Classification)||
Contact Information for " ANTIGEN-BINDING PROTEIN RECOGNIZING MAGE-A4-DERIVED PEPTIDE "
- Mie University Intellectual Property Office
- URL: http://www.crc.mie-u.ac.jp/chizai/index.htm
- Address: 1577, Kurimamachiya-cho, Tsu, Mie, Japan , 514-8507
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