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1. WO2022050725 - METHOD FOR SCREENING IMMUNOGENIC ANTICANCER ACTIVITY CYTOKINE, AND COMPOSITION FOR PREVENTING OR TREATING CANCER DISEASE, COMPRISING IL-15 AS ACTIVE INGREDIENT

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Publication Number WO/2022/050725
Publication Date 10.03.2022
International Application No. PCT/KR2021/011864
International Filing Date 02.09.2021
IPC
C12Q 1/6886 2018.1
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
68involving nucleic acids
6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
6883for diseases caused by alterations of genetic material
6886for cancer
A61K 38/19 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17from animals; from humans
19Cytokines; Lymphokines; Interferons
A61P 35/00 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
A23L 33/135 2016.1
AHUMAN NECESSITIES
23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D91; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
33Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
10using additives
135Bacteria or derivatives thereof, e.g. probiotics
CPC
A23L 33/135
AHUMAN NECESSITIES
23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A23B - A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT
33Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
10using additives
135Bacteria or derivatives thereof, e.g. probiotics
A61K 38/19
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17from animals; from humans
19Cytokines; Lymphokines; Interferons
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
C12Q 1/6886
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms
68involving nucleic acids
6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
6883for diseases caused by alterations of genetic material
6886for cancer
Applicants
  • 재단법인대구경북과학기술원 DAEGU GYEONGBUK INSTITUTE OF SCIENCE AND TECHNOLOGY [KR]/[KR]
  • 경북대학교 산학협력단 KYUNGPOOK NATIONAL UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION [KR]/[KR]
Inventors
  • 백문창 BAEK, Moon-Chang
  • 예경무 YEA, Kyung Moo
  • 강성민 KANG, Sung-Min
Agents
  • 특허법인 태백 TAEBAEK INTELLECTUAL PROPERTY LAW FIRM
Priority Data
10-2020-011277404.09.2020KR
10-2021-011465130.08.2021KR
Publication Language Korean (ko)
Filing Language Korean (KO)
Designated States
Title
(EN) METHOD FOR SCREENING IMMUNOGENIC ANTICANCER ACTIVITY CYTOKINE, AND COMPOSITION FOR PREVENTING OR TREATING CANCER DISEASE, COMPRISING IL-15 AS ACTIVE INGREDIENT
(FR) PROCÉDÉ DE CRIBLAGE DE CYTOKINE À ACTIVITÉ ANTICANCÉREUSE IMMUNITAIRE, ET COMPOSITION POUR LA PRÉVENTION OU LE TRAITEMENT D'UNE MALADIE CANCÉREUSE, COMPRENANT IL-15 EN TANT QUE PRINCIPE ACTIF
(KO) 면역 항암 활성 사이토카인을 스크리닝하는 방법 및 IL-15를 유효성분으로 포함하는 암 질환 예방 또는 치료용 조성물
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Abstract
(EN) The present invention relates to a method for screening a cytokine having immune anticancer activity that inhibits the secretion of exosomes from cancer cells or suppresses the expression of programmed apoptosis ligands, wherein a vector composed of a gene encoding a cytokine, a linker domain encoding a linker, and a transmembrane domain encoding a transmembrane protein transforms into cancer cells, and thus a cytokine exhibiting immune anticancer activity that suppresses the expression level of genes related to exosome secretion or the expression level of PD-L1 can be selected, and the selected cytokine is provided as a new anticancer agent. In addition, the present invention relates to a composition for preventing or treating cancer diseases, the composition comprising IL-15, selected using the above-mentioned screening technique, or an expression promoter or activator thereof as an active ingredient. In the present invention, it was found that treating cancer cells with IL-15 suppresses cancer cell-derived exosome secretion and the expression of PD-L1 inducing immune evasion of T cells, and thereby enhances the anticancer effect, and it was also found that the anticancer effect is directly exhibited on the cancer cells. It was found that IL-15 activates cytotoxic T cells, reduces immune checkpoints PD-1 and CTLA-4, and promotes immune cell-derived exosomes, and thus exhibits an immune anticancer effect. Therefore, IL-15 or an expression promoter or activator thereof can be effectively used as a composition for preventing or treating cancer diseases.
(FR) La présente invention concerne un procédé de criblage d'une cytokine ayant une activité anticancéreuse immunitaire qui inhibe la sécrétion d'exosomes par les cellules cancéreuses ou supprime l'expression de ligands d'apoptose programmée, dans lequel un vecteur composé d'un gène codant une cytokine, d'un domaine de lieur codant un lieur, et d'un domaine transmembranaire codant une protéine transmembranaire est utilisé pour transformer des cellules cancéreuses, et ainsi une cytokine présentant une activité anticancéreuse immunitaire qui supprime le niveau d'expression de gènes liés à la sécrétion d'exosomes ou le niveau d'expression de PD-L1 peut être sélectionnée, et la cytokine sélectionnée est proposée en tant que nouvel agent anticancéreux. De plus, la présente invention concerne une composition pour la prévention ou le traitement de maladies cancéreuses, la composition comprenant IL-15, sélectionnée à l'aide de la technique de criblage mentionnée ci-dessus, ou un promoteur d'expression ou un activateur de celle-ci en tant que principe actif. Dans la présente invention, il a été découvert que le traitement de cellules cancéreuses avec IL-15 supprime la sécrétion d'exosomes dérivés de cellules cancéreuses et l'expression de PD-L1 induisant l'évasion immunitaire des lymphocytes T, et améliore ainsi l'effet anticancéreux, et il a également été découvert que l'effet anticancéreux est directement présenté sur les cellules cancéreuses. Il a été découvert qu'IL-15 active les lymphocytes T cytotoxiques, réduit les points de contrôle immunitaire PD-1 et CTLA-4, et active des exosomes dérivés de cellules immunitaires, et présente ainsi un effet anticancéreux immunitaire. Par conséquent, IL-15 ou un promoteur d'expression ou un activateur de celle-ci peut être efficacement utilisé en tant que composition pour la prévention ou le traitement de maladies cancéreuses.
(KO) 본 발명은 암세포의 엑소좀 분비를 억제하거나 프로그램된 세포사멸-리간드의 발현을 억제하는 면역 항암 활성을 갖는 사이토카인을 스크리닝 하는 방법에 관한 것으로, 사이토카인을 암호화하는 유전자, 링커를 암호화하는 링커 도메인, 및 막관통 단백질을 암호화하는 막관통 도메인으로 구성된 벡터를 암세포에 형질전환함으로써, 엑소좀 분비와 관련된 유전자의 발현 수준 또는 PD-L1의 발현 수준을 억제하는 면역 항암 활성을 나타내는 사이토카인을 선별할 수 있으며, 선별된 사이토카인을 새로운 항암제로 제공한다. 또한, 본 발명은 위의 스크리닝 기법을 이용하여 선별한 IL-15, 이의 발현 촉진제 또는 활성화제를 유효성분으로 포함하는 암 질환 예방 또는 치료용 조성물에 관한 것으로, 본 발명에서는 암세포에 IL-15를 처리 시, 암세포 유래 엑소좀 분비가 억제되고, T 세포의 면역 회피를 유도하는 PD-L1의 발현이 억제되어 항암 효과가 증진되는 것을 확인하였으며, 암세포에 직접적으로 항암 효과를 나타내는 것을 확인하였다. IL-15가 세포독성 T 세포를 활성화시키고 면역관문 PD-1, CTLA-4를 감소시키며 면역세포 유래 엑소좀을 증진시켜 면역 항암 효과를 나타내는 것을 확인하였다. 이는 IL-15, 이의 발현 촉진제 또는 활성화제는 암 질환 예방 또는 치료용 조성물 등으로 유용하게 활용될 수 있다.
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