Russell Pamela J, Hewish Dean, Carter Teresa, Sterling-Levis Katy, Ow Kim, Hattarki Meghan, Doughty Larissa, Guthrie Robin, Shapira Deborah, Molloy Peter L, Werkmeister Jerome A, Kortt Alexander A
Oncology Research Centre, Department of Clinical Medicine, Prince of Wales Hospital, University of New South Wales, NSW 2031 Randwick, Australia.
Cancer Immunol Immunother. 2004 May;53(5):411-21. doi: 10.1007/s00262-003-0457-9. Epub 2004 Jan 13.
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.
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.
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.
Immunoconjugates deliver beneficial effects; further peptide modifications may increase cytotoxicity.
单克隆抗体（MAb）可实现肿瘤靶向治疗，同时将正常组织暴露降至最低。在携带人前列腺癌皮下异种移植瘤的裸鼠中评估了含肽101免疫缀合物的疗效，该肽围绕蜂毒溶血肽的前22个氨基酸设计，以维持两亲性螺旋结构、增强水溶性并提高溶血活性。
使用SPDP将识别人类前列腺癌细胞的小鼠单克隆抗体J591和BLCA-38与肽101交联。利用荷瘤小鼠比较放射性标记免疫缀合物和单克隆抗体的生物分布，或对其进行多次连续注射免疫缀合物。通过肿瘤生长延迟和小鼠存活率提高来评估治疗效果。
放射性标记的免疫缀合物和抗体表现出相似的异种移植瘤嗜性。与单独载体、未缀合抗体及非特异性抗体-肽缀合物相比，全身或瘤内注射免疫缀合物可抑制小鼠肿瘤生长，并提高治疗小鼠的存活率。
免疫缀合物具有有益效果；进一步的肽修饰可能会增加细胞毒性。
