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Treatment and diagnosis of cancer or infectious disease using recognition mechanism of t cell receptor

Foreign code F200010132
Posted date May 22, 2020
Country United States of America
Application number 201716323365
Gazette No. 20190185539
Date of filing Aug 4, 2017
Gazette Date Jun 20, 2019
International application number JP2017028490
International publication number WO2018026018
Date of international filing Aug 4, 2017
Date of international publication Feb 8, 2018
Priority data
  • P2016-154742 (Aug 5, 2016) JP
  • 2017JP28490 (Aug 4, 2017) WO
Title Treatment and diagnosis of cancer or infectious disease using recognition mechanism of t cell receptor
Abstract To provide a therapy and a diagnosis of cancer or an infection using recognition mechanism of a T-cell receptor. An NK cell function enhancer comprises, an active ingredient, a T-cell receptor chimeric protein being a fusion protein of: a T-cell receptor variable region capable of recognizing a cancer-specific antigen or a T-cell receptor variable region capable of recognizing an antigen specific to a pathogen causative of an infection, and an immunoglobulin Fc region, wherein the T-cell receptor chimeric protein binds to an MHC molecular complex of a cancer cell to down-modulate an MHC class I molecule complex, and the cancer cell is killed or damaged by recognition of an NK cell; and an NK cell function enhancer for imparting to an NK cell a function of recognizing a cancer cell or an infected cell infected with a pathogen causative of an infection, which expresses an MHC class I molecule, and killing or damaging the cancer cell or the infected cell by TDCC (T-cell receptor chimeric protein-dependent cellular cytotoxicity) activity.
Outline of related art and contending technology BACKGROUND ART
As cancer treatments, surgical treatments, radiation treatments and chemotherapies are basically known and these are called as major three therapies.
In recent years, in addition to these three major therapies, immunotherapies have been getting attention as a fourth therapy. Examples of immunotherapies include: a method for activating antitumor immunity, which attacks cancer by use of immunocompetence (immune cells) originally possessed by a living body; and a method for blocking immunosuppressive reaction of cancer cells. The former treatments include immunological enhancement by cytokine, enhancement of killer T-cells or NK cells, dendritic cell vaccine therapy and peptide vaccine therapy; and the latter treatments include immune checkpoint inhibition therapy.
As described above, killer T-cells or NK cells are used as a method for activating antitumor immunity. Since NK cells can directly attack cancer, it is known that NK cells are useful in cancer treatment such as antimetastatic (see Non-Patent Literature 1).
T-cells recognize MHCs (major histocompatibility complex) and peptides. T-cells cannot recognize them if MHCs are not expressed in target cells. Meanwhile, NK cells recognize the non-existence of MHCs, and then work. NK cells cannot recognize that MHCs are expressed in target cells. Normal cell usually express MHC molecules, so they cannot become targets of NK cells.
Only NK cells, which do not target cells having an MHC expressed therein, cannot provide a sufficient immunotherapic effect on cancer; and in recent years, researches have been made on use of T-cells capable of specifically recognizing cancer and intensive researches have been made on methods for inducing killer T-cells.
In addition, researches for specifying cancer-specific antigens have been also advanced, and cancer peptide therapy or dendritic cell therapy has been developed.
T-cell receptors (TCR) perform an important role on the action of T-cells; and recent years have witnessed the development of a method for analyzing a T-cell receptor repertoire of a T-cell receptor of a patient with a certain disease and identifying a disease-specific T-cell receptor. Further, a method that uses a protein having a fragment of a T-cell receptor has been also reported (see Patent Literature 1).
As is the case with cancer, for infectious diseases, in particular, emerging/reemerging infectious diseases, for which treatments have not been established, there are expectations on immunotherapies using abilities of NK cells or T-cells for eliminating infected cells.
Scope of claims [claim1]
1. An NK cell function enhancer comprising, as an active ingredient, a T-cell receptor chimeric protein being a fusion protein of a T-cell receptor variable region capable of recognizing a cancer-specific antigen and an immunoglobulin Fc region,
wherein the T-cell receptor chimeric protein binds to an MHC molecular complex of a cancer cell to reduce the expression of an MHC class I molecular complex and the cancer cell is killed or damaged by recognition of an NK cell or
wherein the enhancer is for imparting a recognition function of a cancer cell expressing an MHC class I molecule to an NK cell to kill or damage the cancer cell by TDCC (T-cell receptor chimeric protein-dependent cellular cytotoxicity) activity.

[claim2]
2. (canceled)

[claim3]
3. The NK cell function enhancer according to claim 1, wherein the T-cell receptor chimeric protein comprises all of the T-cell receptor variable region and CDR3, and a J region.

[claim4]
4. The NK cell function enhancer according to claim 1, wherein the T-cell receptor variable region is an α chain and/or β chain of the T-cell receptor.

[claim5]
5. (canceled)

[claim6]
6. The NK cell function enhancer according to claim 1, wherein the immunoglobulin Fc region is an Fc region of IgG.

[claim7]
7. The NK cell function enhancer according to claim 1, wherein the enhancer is a dimer consisting of two fusion proteins of the T-cell receptor variable region and the immunoglobulin Fc region and the two proteins are bonded to each other by disulfide bond.

[claim8]
8. The NK cell function enhancer according to claim 1, wherein the T-cell receptor binds to an MHC class I molecule.

[claim9]
9.-12. (canceled)

[claim10]
13. A complex comprising a T-cell receptor chimeric protein capable of recognizing a cancer-specific antigen, and an NK cell receptor.

[claim11]
14. (canceled)

[claim12]
15. An NK cell function enhancer comprising, as an active ingredient, a T-cell receptor chimeric protein being a fusion protein of a T-cell receptor variable region capable of recognizing an antigen specific to a pathogen causative of an infection, and an immunoglobulin Fc region,
wherein the T-cell receptor chimeric protein binds to an MHC class I molecular complex of an infected cell infected with the pathogen causative of the infection to reduce the expression of an MHC molecular complex and the infected cell is killed or damaged by recognition of an NK cell, or
wherein the enhancer is for imparting a recognition function of an infected cell infected with the pathogen causative of the infection, which expresses an MHC class I molecule, to an NK cell, and killing or damaging the infected cell by TDCC (T-cell receptor chimeric protein-dependent cellular cytotoxicity) activity.

[claim13]
16. (canceled)

[claim14]
17. The NK cell function enhancer according to claim 15, wherein the T-cell receptor chimeric protein comprises all of the T-cell receptor variable region and CDR3, and a J region.

[claim15]
18. The NK cell function enhancer according to claim 15, wherein the T-cell receptor variable region is an α chain and/or β chain of the T-cell receptor.

[claim16]
19. (canceled)

[claim17]
20. The NK cell function enhancer according to claim 15, wherein the immunoglobulin Fc region is an Fc region of IgG.

[claim18]
21. The NK cell function enhancer according to claim 15, wherein the enhancer is a dimer consisting of two fusion proteins of the T-cell receptor variable region and the immunoglobulin Fc region and the two proteins are bonded to each other by disulfide bond.

[claim19]
22. The NK cell function enhancer according to claim 15, wherein the T-cell receptor binds to an MHC class I molecule.

[claim20]
23.-26. (canceled)

[claim21]
27. A complex comprising a T-cell receptor chimeric protein capable of recognizing an antigen specific to a pathogen causative of an infectious disease, and an NK cell receptor.

[claim22]
28.-54. (canceled)
  • Inventor, and Inventor/Applicant
  • OGASAWARA KOETSU
  • TOHOKU UNIVERSITY
IPC(International Patent Classification)
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