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Genetically Engineered Cell-Derived Nanoparticles for Targeted Breast Cancer Immunotherapy.
Molecular Therapy ( IF 12.1 ) Pub Date : 2019-11-27 , DOI: 10.1016/j.ymthe.2019.11.020 Xiaojing Shi 1 , Qinqin Cheng 1 , Tianling Hou 1 , Menglu Han 1 , Goar Smbatyan 2 , Julie E Lang 3 , Alan L Epstein 4 , Heinz-Josef Lenz 2 , Yong Zhang 5
Molecular Therapy ( IF 12.1 ) Pub Date : 2019-11-27 , DOI: 10.1016/j.ymthe.2019.11.020 Xiaojing Shi 1 , Qinqin Cheng 1 , Tianling Hou 1 , Menglu Han 1 , Goar Smbatyan 2 , Julie E Lang 3 , Alan L Epstein 4 , Heinz-Josef Lenz 2 , Yong Zhang 5
Affiliation
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Exosomes are nanosized membranous vesicles secreted by a variety of cells. Due to their unique and pharmacologically important properties, cell-derived exosome nanoparticles have drawn significant interest for drug development. By genetically modifying exosomes with two distinct types of surface-displayed monoclonal antibodies, we have developed an exosome platform termed synthetic multivalent antibodies retargeted exosome (SMART-Exo) for controlling cellular immunity. Here, we apply this approach to human epidermal growth factor receptor 2 (HER2)-expressing breast cancer by engineering exosomes through genetic display of both anti-human CD3 and anti-human HER2 antibodies, resulting in SMART-Exos dually targeting T cell CD3 and breast cancer-associated HER2 receptors. By redirecting and activating cytotoxic T cells toward attacking HER2-expressing breast cancer cells, the designed SMART-Exos exhibited highly potent and specific anti-tumor activity both in vitro and in vivo. This work demonstrates preclinical feasibility of utilizing endogenous exosomes for targeted breast cancer immunotherapy and the SMART-Exos as a broadly applicable platform technology for the development of next-generation immuno-nanomedicines.
中文翻译：
基因工程细胞衍生纳米粒子用于靶向乳腺癌免疫治疗。
外来体是由多种细胞分泌的纳米级膜状囊泡。由于其独特的和药理上重要的特性，细胞衍生的外来体纳米颗粒引起了对药物开发的极大兴趣。通过用两种不同类型的表面展示单克隆抗体基因修饰外泌体，我们开发了一种外泌体平台，称为合成多价抗体重靶向外泌体（SMART-Exo），用于控制细胞免疫。在这里，我们通过工程化外泌体通过抗人CD3和抗人HER2抗体的遗传展示，将这种方法应用于表达人表皮生长因子受体2（HER2）的乳腺癌，从而导致SMART-Exos双重靶向T细胞CD3和乳腺癌相关的HER2受体。通过重定向和激活细胞毒性T细胞使其攻击表达HER2的乳腺癌细胞，设计的SMART-Exos在体外和体内均表现出高度有效的特异性抗肿瘤活性。这项工作证明了利用内源性外泌体进行靶向乳腺癌免疫治疗的临床前可行性，并将SMART-Exos作为开发下一代免疫纳米药物的广泛适用的平台技术。
更新日期：2019-11-28
中文翻译：
基因工程细胞衍生纳米粒子用于靶向乳腺癌免疫治疗。
外来体是由多种细胞分泌的纳米级膜状囊泡。由于其独特的和药理上重要的特性，细胞衍生的外来体纳米颗粒引起了对药物开发的极大兴趣。通过用两种不同类型的表面展示单克隆抗体基因修饰外泌体，我们开发了一种外泌体平台，称为合成多价抗体重靶向外泌体（SMART-Exo），用于控制细胞免疫。在这里，我们通过工程化外泌体通过抗人CD3和抗人HER2抗体的遗传展示，将这种方法应用于表达人表皮生长因子受体2（HER2）的乳腺癌，从而导致SMART-Exos双重靶向T细胞CD3和乳腺癌相关的HER2受体。通过重定向和激活细胞毒性T细胞使其攻击表达HER2的乳腺癌细胞，设计的SMART-Exos在体外和体内均表现出高度有效的特异性抗肿瘤活性。这项工作证明了利用内源性外泌体进行靶向乳腺癌免疫治疗的临床前可行性，并将SMART-Exos作为开发下一代免疫纳米药物的广泛适用的平台技术。
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