卵巢癌腹水抗腺相关病毒2 (AAV)抗体谱:对AAV腹腔内基因治疗的意义

J. Skubis-Zegadło, M. Kowalska, B. Śpiewankiewicz, Wacław Smiert Krzysztof Gawrychowski, M. Małecki
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引用次数: 1

摘要

目的:重组腺相关病毒(rAAV) 2型是基因治疗中常用的载体。然而,抗aav2中和抗体或其他中和因子的存在会显著限制有效转导。腹腔内基因治疗可以使靶基因直接局部递送到卵巢癌细胞。到目前为止,还没有关于腹水中存在抗aav抗体的报道,这可能限制了rAAV作为腹膜内基因治疗候选载体的有效性。因此,腹水中预先存在的中和抗体的表征将为成功的腹膜内基因治疗提供见解。方法:对23例3期和4期卵巢癌患者的腹水样本进行研究。采集标本,采用ELISA法检测抗aav抗体的存在,中和法检测中和抗体的存在。结果:我们的结果表明,抗raav抗体存在于70%的腹水样本中,而中和因子/抗体存在于78%的腹水样本中。这种相关性为腹水中存在其他与抗体不同的未知因素提供了证据,这些因素能够在缺乏抗aav抗体的情况下抑制AAV2感染。结论:腹水中是否存在针对rAAV的中和抗体或其他中和因子,可能会限制以rAAV为载体进行腹水基因治疗的有效性,因此在进行腹水基因治疗时应考虑这些抗体的存在。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti Adeno-Associated Virus 2 (AAV) Antibody Profile in Ovarian Cancer Ascitic Fluid: Implications for AAV Intraperitoneal Gene Therapy
Objective: Recombinant adeno-associated virus (rAAV) type 2 is a common vector used in gene therapy. However, the presence of anti-AAV2 neutralizing antibodies or other neutralizing factors can significantly limit effective transduction. Intraperitoneal gene therapy could enable local delivery of the target gene directly to ovarian cancer cells. Until now, there have been no reports on the presence of anti-AAV antibodies in ascitic fluid, which might limit the effectiveness of rAAV as a candidate vector for intraperitoneal gene therapy. Thus, the characterization of the preexisting neutralization antibodies in ascitic fluid will provide insight into successful intraperitoneal gene therapy. Methods: The study was conducted on 23 ascitic fluid samples obtained from women with stage 3 and 4 ovarian cancer. The samples were collected to determine the presence of anti-AAV antibodies with ELISA test and the presence of neutralizing antibodies with neutralizing assay. Results: Our results indicate that anti-rAAV antibodies are present in 70%, whereas neutralizing factors/antibodies are present in 78% of analyzed ascitic fluid samples. This correlation provides evidence for the presence of additional, different from antibodies, currently unknown factors in ascites, which are able to inhibit AAV2 infection in the absence of anti-AAV antibodies. Conclusion: The presence of neutralizing antibodies against rAAV or other neutralizing factors in ascitic fluid should be taken into account during intraperitoneal gene therapy, because they might limit effective intraperitoneal gene therapy with rAAV as a vector.
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