|
- 现金
- 329 元
- 精华
- 1
- 帖子
- 231
- 注册时间
- 2001-12-25
- 最后登录
- 2004-2-29
|
1楼
发表于 2002-3-12 08:16
HBV感染治疗中一极有希望的治疗方法----静注用抗HBS抗体
干扰素无反应，贺普丁无效或耐药或停药反跳，因此有必要再找治乙肝新法。
抗HBS抗体在国内仅肌注，主要用于乙型肝炎的预防，而应用于乙肝治疗是近年来的一“另富新义”件事。
治疗性疫苗中利用抗HBS抗体球蛋白上Fc片段与APC上的Fc受体结合，故将与抗体结合的抗原（疫苗，免疫原）一起吞入APC胞内，而诱生针对抗原的特异性细胞与体液免疫反应。
利用上述原理，美国最近利用可静注的二抗HBS特异性单克隆抗体组成的混合制剂HBV-AB(XTL). 发现单一剂量0.26 mg (260 IU) to 40 mg (40,000 IU)中，在1:2 to 1:20 的 Ab:Ag 分子比可致HBS AG下降至测不出来，而且同时伴相应的HBV DNA下降。而采用4 weekly infusions of 10, 20, 40, or 80mg 的实验发现，可致HBS AG和HBVＤＮＡ明显下降。二种方案中可静注的二抗HBS特异性单克隆抗体组成的混合制剂HBV-AB(XTL)均无不良反应反生。因此此法综合应用于抗HBV的免疫或化学治疗中将更加有效提高效果并防止复发。
依本版主的知识面，我认为应从免疫感应和效应二过程来研究不同类型的抗HBS抗体如IgG、IgM型anti-HBs对HBV感染的治疗效果，还应结合机体对HBC AG的反应来研究其对HBS AG的反应的影响。当然目前对HBV感染中免疫反应的研究仅多限于免疫效应的研究尤T细胞和NK细胞，而对具有免疫感应和效应双功能的B细胞、单核巨噬细胞和主要起免疫感应作用的树突状细胞缺乏深入的研究。而且就本版主的知识，目前的对HBV感染中T细胞和NK细胞变化的研究仅限于其数目变化，而对Th0\1\2\3...(Th/Ti)和Tc0\1\2\3...(Tc/Ts)数目和功能研究不多。事实上，本版主发现慢性HBV携带者、乙型肝炎和肝硬化及肝癌中T细胞亚类（数目）变化完全不同，与以往报道完全不一致（初步结果参见我们的一研究快报，其他结果正在整理中）。
Hepatology 2002 Mar;35(3):673-679
Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties.
Galun E, Eren R, Safadi R, Ashour Y, Terrault N, Keeffe EB, Matot E, Mizrachi S, Terkieltaub D, Zohar M, Lubin I, Gopher J, Shouval D, Dagan S. Goldyne Savad
Institute of Gene Therapy, Hadassah University Hospital; XTL Biopharmaceuticals Ltd., Rehovot; Liver Unit, Hadassah University Hospital, Jerusalem, Israel; University of California at San Francisco, San Francisco, CA, and Stanford University Medical Center, Stanford, CA.
Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers.
PMID: 11870383
Gut 2002 Jan;50(1):95-9
Comment in: Gut. 2002 Jan;50(1):7-8.
Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
Roque-Afonso AM, Feray C, Samuel D, Simoneau D, Roche B, Emile JF, Gigou M, Shouval D, Dussaix E.
Laboratoire de Virologie, Hopital Paul Brousse, Universite Paris-Sud UPRES 1596, 12 avenue Paul Vaillant Couturier, 94804 Villejuif, France. [email protected] BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.
PMID: 11772974
[ 此消息由 medline 在 2002-03-17.18:24:48 编辑过 ] |
|
