WO2021261891A1 - 박테리아 세포밖 소포체의 암 치료 효능 증진 방법 및 조성 - Google Patents
박테리아 세포밖 소포체의 암 치료 효능 증진 방법 및 조성 Download PDFInfo
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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Abstract
Description
Component | Concentration |
Salts and glucose | |
Na2HPO4·2H2O | 42.3 mM |
KH2PO4 | 22.0 mM |
NH4Cl | 9.4 mM |
NaCl | 8.6 mM |
MgSO4·7H2O | 1.0 mM |
CaCl2·2H2O | 0.3 mM |
Glucose | 0.4% |
Vitamins | |
Thiamine | 3.0 μM |
Biotin | 4.1 μM |
Trace elements | |
EDTA | 0.2 mM |
FeCl3 | 30.7 μM |
ZnCl2 | 6.2 μM |
CuCl2·2H2O | 0.8 μM |
CoCl2·6H2O | 0.4 μM |
H3BO3 | 1.6 μM |
MnCl2 ·4H2O | 81.0 nM |
Group # | PBS or Ab | PBS or EV |
1 | PBS | PBS |
2 | PBS | EV (0.2 μg) |
3 | Ab (50 μg) | PBS |
4 | Ab (50 μg) | EV (0.2 μg) |
Size (nm) | Concentration | Total amount | |||
Protein (mg/mL) | Particle (x1012/mL) | Protein (mg) | Particle (x1012) | ||
CMDVVP-LB | 156.8 ± 61.2 | 5.3 | 28.7 | 5.3 | 28.7 |
OMDVVP-LB | 127.6 ± 42.8 | 2.3 | 24.6 | 2.5 | 27.3 |
Group # | Sample |
1 | Vehicle-1 (for EVVP-LB) |
2 | EVVP-LB 5 μg |
3 | Vehicle-2 (for CMDVVP-LB and OMDVVP-LB) |
4 | CMDVVP-LB 10 μg |
5 | OMDVVP-LB 10 μg |
Claims (27)
- 박테리아 세포밖 소포체(extracellular vesicle) 및 면역 관문 억제제(immune checkpoint inhibitor)를 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물.
- 제1항에 있어서, 상기 박테리아는 그람 음성 박테리아 또는 그람 양성 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제2항에 있어서, 상기 그람 음성 박테리아는 이스체리치아(Escherichia) 속, 헬리코박터(Helicobcater) 속, 헤모필루스(Hemophilus) 속, 나이세리아(Neisseria) 속, 시아노박테리움(Cyanobacterium) 속, 크렙시엘라(Klebsiella) 속, 아세토박터(Acetobacter) 속, 아시네토박터(Acinetobacter) 속, 엔테로박터(Enterobacter) 속, 클라미디아(Chlamydia) 속, 비브리오(Vibrio) 속, 슈도모나스(Pseudomonas) 속, 살모넬라(Salmonella) 속, 티오박터(Thiobacter) 속, 보렐리아(Borrelia) 속, 부르크홀데리아(Burkholderia) 속, 세라티아(Serratia) 속 및 트레포네마(Treponema) 속으로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제2항에 있어서, 상기 그람 양성 박테리아는 바실러스(Bacillus) 속, 노카르디아(Nocardia) 속, 클로스트리듐(Clostridium) 속, 프로피오니박테리움(Propionibacterium) 속, 악티노마이세스(Actinomyces) 속, 엔테로코커스(Enterococcus) 속, 코리네박테리움(Corynebacterium) 속, 리스테리아(Listeria) 속, 락토바실러스(Lactobacillus) 속, 가드네렐라(Gardnerella) 속, 마이코박테리움(Mycobacterium) 속, 마이코플라스마(Mycoplasma) 속, 스타필로코커스(Staphylococcus) 속, 스트렙토마이세스(Streptomyces) 속, 마이크로코커스(Micrococcus) 속 및 스트렙토코커스(Streptococcus) 속으로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 박테리아는 형질 전환된 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제5항에 있어서, 상기 박테리아는 세포밖 소포체의 독성이 약화되도록 형질 전환된 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제5항에 있어서, 상기 박테리아는 내독소 생성 유전자가 결손되거나 변형된 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제5항에 있어서, 상기 박테리아는 특이 세포 또는 조직으로 타겟팅되도록 형질 전환된 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 박테리아는 화학 조성 배지에서 배양된 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제9항에 있어서, 상기 화학 조성 배지는 M9 배지(M9 medium), DMEM 배지(Dulbecco's modified Eagle's medium) 및 RPMI 1640 배지(Roswell Park Memorial Institute medium 1640)로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제5항에 있어서, 상기 박테리아는 세포 접합 분자, 항체, 표적 유도 단백질, 세포막 융합 물질, 또는 이들의 융합 단백질로 이루어진 군에서 선택되는 하나 이상을 발현되도록 형질 전환된 박테리아인 것을 특징으로 하는 약학적 조성물.
- 제11항에 있어서, 상기 세포막 융합 물질이 인간 EGF(human epidermal growth factor)인 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 박테리아 세포밖 소포체의 막이 상기 박테리아의 세포막 이외의 성분을 추가로 포함하는 것을 특징으로 하는 약학적 조성물.
- 제13항에 있어서, 상기 박테리아의 세포막 이외의 성분이 표적 유도 물질, 세포막 융합 물질, 사이클로덱스트린, 폴리에틸렌글리콜로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 박테리아 세포밖 소포체의 막 성분이 화학적으로 변형된 것을 특징으로 하는 약학적 조성물.
- 제15항에 있어서, 상기 박테리아 세포밖 소포체의 막 성분이 티올기 또는 아민기를 이용한 화학적 변형되거나, 상기 박테리아 세포밖 소포체에 폴리에틸렌글리콜을 화학적으로 결합시킨 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 박테리아 세포밖 소포체는 초고속원심분리, 밀도 구배 초고속원심분리, 한외여과법, 크기 배제 크로마토그래피, 이온교환 크로마토그래피, 면역친화성 분리법, 미세유체기술 분리법, 수성 2상 시스템 및 폴리머 기반 침전법으로 이루어진 군에서 선택된 방법으로 분리된 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 면역 관문 억제제는 PD1(programmed cell death-1) 길항제, PDL1(programmed cell death-ligand 1) 길항제, PDL2(programmed cell death-ligand 2) 길항제, CD27(cluster of differentiation 27) 길항제, CD28(cluster of differentiation 28) 길항제, CD70(cluster of differentiation 70) 길항제, CD80(cluster of differentiation 80) 길항제, CD86(cluster of differentiation 86) 길항제, TIGIT (T cell immunoreceptor with Ig and ITIM domains) 길항제, CD137(cluster of differentiation 137) 길항제, CD276(cluster of differentiation 276) 길항제, KIRs(killer-cell immunoglobulin-like receptors) 길항제, LAG3(lymphocyte-activation gene 3) 길항제, TNFRSF4(tumor necrosis factor receptor superfamily, member 4) 길항제, GITR(glucocorticoid-induced TNFR-related protein) 길항제, GITRL(glucocorticoid-induced TNFR-related protein ligand) 길항제, 4-1BBL(4-IBB ligand) 길항제, CTLA4(cytotoxic T lymphocyte associated antign-4) 길항제, A2aR(adenosine A2A receptor) 길항제, VTCN1(V-set domain-containing T-cell activation inhibitor 1) 길항제, BTLA(B- and T-lymphocyte attenuator) 길항제, IDO(indoleamine 2,3-dioxygenase) 길항제, TIM3(T-cell immunoglobulin domain and mucin-domain containing-3) 길항제, VISTA(V-domain Ig suppressor of T cell activation) 길항제, 및 KLRA(killer cell lectin-like receptor subfamily A) 길항제 및 이들의 조합으로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제18항에 있어서, 상기 면역 관문 억제제는 단백질, 펩타이드, 항체, 이의 항원 결합 단편, 또는 억제 핵산인 것을 특징으로 하는 약학적 조성물.
- 제19항에 있어서, 상기 억제 핵산은 siRNA, shRNA, 또는 안티센스 RNA인 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 면역 관문 억제제는 더발루맙(Durvalumab), 아테졸리주맙(Atezolizumab), 아벨루맙(Avelumab), 트리멜리무맙(Tremelimumab), 이필리무맙(Ipilimumab), 펨브롤리주맙(Pembrolizumab), 니볼루맙(Nivolumab), 피딜리주맙(Pidilizumab), BMS986016, 세미프리맙(Cemiplimab) 및 릴리루맙(lirilumab)으로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 박테리아 세포밖 소포체와 면역 관문 억제제는 동시에, 순차적으로 또는 별도로 병용 투여되는 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 암은 위암, 폐암, 비소세포성 폐암, 유방암, 난소암, 간암, 기관지암, 비인두암, 후두암, 췌장암, 대장암, 방광암, 결장암, 자궁경부암, 골암, 비소세포성 골암, 혈액암, 피부암, 두부 또는 경부 암, 자궁암, 직장암, 항문 부근암, 결장암, 나팔관암, 자궁내막암, 질암, 음문암, 호지킨병(Hodgkin's disease), 식도암, 소장암, 내분비선암, 갑상선암, 부갑상선암, 부신암, 연조직 육종, 요도암, 음경암, 전립선암, 만성 또는 급성 백혈병, 림프구 림프종, 신장 또는 수뇨관암, 신장세포암종, 신장골반암종, 침샘암, 육종암, 가성점액종, 간모세포종, 고환암, 교모세포종, 구순암, 난소생식세포종양, 기저세포암, 다발성골수종, 담낭암, 맥락막흑색종, 바터팽대부암, 복막암, 설암, 소세포암, 소아림프종, 신경모세포종, 십이지장암, 요관암, 성상세포종, 수막종, 신우암, 외음부암, 흉선암, 중추신경계(central nervous system, CNS) 종양, 1차 중추신경계 림프종, 척수종양, 뇌간 신경교종 및 뇌하수체 선종으로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 제1항에 있어서, 상기 약학적 조성물은 인간을 비롯한 포유동물에 경구적인 방법 또는 비경구적인 방법으로 투여하는 것인 약학적 조성물.
- 제24항에 있어서, 상기 비경구적인 방법은 정맥 내, 근육 내, 동맥 내, 골수 내, 경막 내, 심장 내, 경피, 피하, 복강 내, 비강 내, 장관, 국소, 설하 및 직장 내 투여로 이루어진 군에서 선택되는 것을 특징으로 하는 약학적 조성물.
- 암 치료제를 제조하기 위한 박테리아 세포밖 소포체(extracellular vesicle) 및 면역 관문 억제제(immune checkpoint inhibitor)의 용도.
- 박테리아 세포밖 소포체(extracellular vesicle) 및 면역 관문 억제제(immune checkpoint inhibitor)를 유효성분으로 포함하는 조성물의 유효량을 이를 필요로 하는 개체에 투여하는 것을 포함하는 암 치료 방법.
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP21829916.2A EP4169520A1 (en) | 2020-06-22 | 2021-06-22 | Method and composition for enhancing cancer treatment efficacy of bacteria extracellular vesicles |
CN202180051621.0A CN116056723A (zh) | 2020-06-22 | 2021-06-22 | 增强细菌胞外囊泡的癌症治疗效果的方法和组合物 |
JP2022579808A JP2023531529A (ja) | 2020-06-22 | 2021-06-22 | バクテリア細胞外小胞体の癌治療効能を増進する方法及び組成物 |
KR1020227044481A KR20230027050A (ko) | 2020-06-22 | 2021-06-22 | 박테리아 세포밖 소포체의 암 치료 효능 증진 방법 및 조성 |
US18/012,498 US20230248783A1 (en) | 2020-06-22 | 2021-06-22 | Method and composition for enhancing cancer treatment efficacy of bacteria extracellular vesicles |
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CN114712496A (zh) * | 2022-04-29 | 2022-07-08 | 中山大学·深圳 | 一种展示新抗原的细菌衍生外膜囊泡疫苗及制备方法和在制备癌症免疫治疗试剂盒中的应用 |
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CN114404571A (zh) * | 2022-01-20 | 2022-04-29 | 中山大学·深圳 | 一种装载化疗药物且tigit过表达的工程化载药细胞膜囊泡以及制备方法和应用 |
CN114712496A (zh) * | 2022-04-29 | 2022-07-08 | 中山大学·深圳 | 一种展示新抗原的细菌衍生外膜囊泡疫苗及制备方法和在制备癌症免疫治疗试剂盒中的应用 |
CN114712496B (zh) * | 2022-04-29 | 2023-10-13 | 中山大学·深圳 | 一种展示新抗原的细菌衍生外膜囊泡疫苗及制备方法和在制备癌症免疫治疗试剂盒中的应用 |
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EP4169520A1 (en) | 2023-04-26 |
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