KR20120091266A - T-세포 매개성 질환의 치료 방법 - Google Patents
T-세포 매개성 질환의 치료 방법 Download PDFInfo
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- KR20120091266A KR20120091266A KR1020127014047A KR20127014047A KR20120091266A KR 20120091266 A KR20120091266 A KR 20120091266A KR 1020127014047 A KR1020127014047 A KR 1020127014047A KR 20127014047 A KR20127014047 A KR 20127014047A KR 20120091266 A KR20120091266 A KR 20120091266A
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Abstract
Description
도 2. 항-CD3 OKT3 항체로 자극화한 후 12일 후에 종양 괴사 인자 α(TNFα) 및 IL-16의 TriPS 세포로부터의 분비 저해를 나타낸 막대 그래프. 인간 모유(HC) 2626(MR-DKP 포함함) 밴드 DA-DKP에 의한 TNFα 및 IL-16의 분비 저해를 나타낸다. 고농도의 인간 모유의 용해 작용으로 인해, 최대 분비는 HC2626을 1:100 및 1:1000 희석액으로 사용하였을때 관찰되었다. 0.5 mM DA-DKP를 이용한 경우 용해가 관찰되지 않았으며 TNFα 및 IL-16 분비가 감소되었다.
도 3. 항-CD3 OKT3 항체를 이용하여 자극화한 다음 10일후 TriPS 세포로부터 TNFα 분비 저해를 나타낸 막대그래프이다. HC 2626에서 보여진 바와 같이, HC RBL 및 DA-DKP는 적정 반응에 대해 추가적으로 평가되어져야 함을 나타낸다. 강력한 활성을 나타낼 수 있다.
도 4. 항-CD3 OKT3 항체를 이용하여 자극화한 후 여러가지 시간대에 TriPS 세포로부터의 TNFα 분비 저해를 나타낸 막대 그래프이다. 자극 주기의 초기에, DA-DKP 및 HC RBL 효과는 저해적이이나, 주기 후기(14일)에는 자극적인 효과를 나타낸다. HC 2626은 모든 시간 대에서 저해하는데, 이는 아마 다른 성분들로 인한 것이다.
도 5. 항-CD3 OKT3 항체를 이용하여 자극화한 후 7-10일 후에 H4#9.25 세포(마이엘린계 단백질에 특이적인 다발 경화증 환자의 부검 뇌 조직으로부터 분리한 D4+ T 세포 주)로부터의 TNFα 분비저해를 나타낸 막대 그래프이다. 상기 T 세포주로부터의 TNFα 분비는 또한 HC 2626, HC RBL 및 DA-DKP에 의해 저해됨을 나타낸다.
번호 | 약어 | 화합물 |
1 | Akt 1/2 | 단백질 키나제 B, 항-세포자살성 키나제 |
2 | c-Cb1 | TcR 저해 경로; Tyr292 인산화는 Syk 및 ZAP-70의 결합 및 불활성화를 활성화함. |
3 | CBP | csk 결합 단백질(PAG); csk를 분비하기 위한 통합 막 단백질 일시적 (및 저농도) Tyr-de-인산화 |
4 | CREB | cAMP 반응 요소 결합 단백질; IL-2 프로모터의 활성화/하향 조절을 위한, POated(unk) |
5 | csk | COOH-말단 src 키나제; Ser364-인산화, Tyr-인산화(활성)는 lck를 인산화 및 불활성화함. |
6 | ERK | 세포외 신호 관련 키나제 |
7 | c-fos | TcR 자극에 의해 활성화된 AP-1 성분; N- 및 C-unk 잔기 둘다에 인산화 |
8 | NFATC | 활성화된 T 세포의 핵 인자; 무활성의 순수 상태 |
9 | c-jun | TcR 활성화에 의해 활성화된 AP-1 성분; JNK-MAPK에 의해 Ser63에 인산화 |
10 | IκB-α | NFκB의 저해자 |
11 | pIκB-α | 세린 인산화 및 NFκB 저해자 불활성화 |
12 | p38 MAPK | 미토겐-활성화 단백질 키나제 |
13 | pI3 키나제/p85 | 글루코코르티코이드 및 베타2-아드레날린성-R에 의해 활성화됨 |
14 | pten | 세포질 3'-이노시톨 포스파타제; 종양 억제 유전자는 PI-PO를 무활성의 형태로 변환함으로서 PI3' 키나제에 길항작용한다. |
15 | c-Raf-1 | |
16 | Rap1 | 음성적인 TcR 조절성 GTPase |
17 | Ras | 키나제; 아네르기중에 불활성화됨 |
18 | fyn | 세포막 결합된 즉각 TcR 신호 키나제 |
19 | lck | 세포막 결합된 즉각 TcR 신호 키나제, 활성형은 Tyr395 인산화된 형태; |
20 | ZAP70키나제 | CD3ζ으로부터시그널; POated at ? lk/fyn, ZAP70 POates LAT(T 세포 활성화에 대한 링커) at Tyr's and Tyr's on SLP-76 |
Claims (12)
- 단백질 또는 펩티드 용액의 여과액을 포함하는 약학 조성물로서, 상기 여과액은, 알부민, 면역글로불린, 및 에리트로포이에틴으로 이루어진 군으로부터 선택되는 단백질을 체류시키는 분획 분자량을 가진 한외여과막으로 상기 단백질 또는 펩티드 용액을 통과시켜 생산되고, 상기 여과액은 YE-DKP, MR-DKP 및 DA-DKP로 이루어진 군으로부터 선택되는 디케토피페라진을 함유하는 것을 특징으로 하는 약학 조성물.
- 제1항에 있어서, 상기 여과액은 3000 미만의 분자량을 갖는 성분을 함유하는 조성물.
- 제1항에 있어서, 상기 단백질 또는 펩티드는 인간 단백질 또는 펩티드인 조성물.
- 제1항에 있어서, 상기 단백질 또는 펩티드는 인간 알부민인 조성물.
- 제2항에 있어서, 상기 단백질 또는 펩티드는 인간 단백질 또는 펩티드인 조성물.
- 제2항에 있어서, 상기 단백질 또는 펩티드는 인간 알부민인 조성물.
- 단백질 또는 펩티드 용액의 여과액으로서, 상기 여과액은, 알부민, 면역글로불린, 및 에리트로포이에틴으로 이루어진 군으로부터 선택되는 단백질을 체류시키는 분획 분자량을 가진 한외여과막으로 상기 단백질 또는 펩티드 용액을 통과시켜 생산되고, 상기 여과액은 YE-DKP, MR-DKP 및 DA-DKP로 이루어진 군으로부터 선택되는 디케토피페라진을 함유하는 것을 특징으로 하는 여과액.
- 제7항에 있어서, 상기 여과액은 3000 미만의 분자량을 갖는 성분을 함유하는 여과액.
- 제7항에 있어서, 상기 단백질 또는 펩티드는 인간 단백질 또는 펩티드인 여과액.
- 제7항에 있어서, 상기 단백질 또는 펩티드는 인간 알부민인 여과액.
- 제8항에 있어서, 상기 단백질 또는 펩티드는 인간 단백질 또는 펩티드인 여과액.
- 제8항에 있어서, 상기 단백질 또는 펩티드는 인간 알부민인 여과액.
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