Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies
Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies
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DOI：
10.1007/s00262-003-0457-9
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Kortt, AA
中科院分区：
文献类型：
--
作者：
Russell, PJ;Hewish, D;Kortt, AA
背景：单克隆抗体（MAb）可以针对肿瘤进行靶向治疗，同时最大限度地减少正常组织的暴露。在带有皮下人前列腺癌异种移植物的裸鼠中评估了含有肽 101 的免疫缀合物的功效，肽 101 是围绕蜂毒（蜂毒肽）的前 22 个氨基酸设计的，以维持两亲性螺旋、增强水溶性和增加溶血活性。方法：使用识别人前列腺癌细胞的小鼠 MAb、J591 和 BLCA-38 与肽 101 交联社会民主党。荷瘤小鼠用于比较放射性标记的免疫缀合物和 MAb 的生物分布，或接受多次连续注射免疫缀合物。通过延迟肿瘤生长和增加小鼠存活率来评估治疗效果。结果：放射性标记的免疫缀合物和抗体显示出相似的异种移植趋向性。相对于单独的载体、未缀合的抗体和非特异性抗体-肽缀合物，全身或肿瘤内注射免疫缀合物可抑制小鼠的肿瘤生长，并提高治疗小鼠的存活率。进一步的肽修饰可能会增加细胞毒性。
Background: Monoclonal antibodies (MAbs) can target therapy to tumours while minimising normal tissue exposure. Efficacy of immunoconjugates containing peptide 101, designed around the first 22 amino acids of bee venom, melittin, to maintain the amphipathic helix, to enhance water solubility, and to increase hemolytic activity, was assessed in nude mice bearing subcutaneous human prostate cancer xenografts.Methods: Mouse MAbs, J591 and BLCA-38, which recognise human prostate cancer cells, were cross-linked to peptide 101 using SPDP. Tumour-bearing mice were used to compare biodistributions of radiolabeled immunoconjugates and MAb, or received multiple sequential injections of immunoconjugates. Therapeutic efficacy was assessed by delay in tumour growth and increased mouse survival.Results: Radiolabeled immunoconjugates and antibodies showed similar xenograft tropism. Systemic or intratumoural injection of immunoconjugates inhibited tumour growth in mice relative to carrier alone, unconjugated antibody and nonspecific antibody-peptide conjugates and improved survival for treated mice.Conclusions: Immunoconjugates deliver beneficial effects; further peptide modifications may increase cytotoxicity.