Lee Daniel Y, Lim Kwang Suk, Valencia Gabriel M, Jung Minjin, Bull David A, Won Young-Wook
Division of Cardio-Thoracic Surgery Department of Surgery University of Utah School of Medicine Salt Lake City UT 84132 USA.
Division of Cardio-Thoracic Surgery Department of Surgery University of Arizona College of Medicine Tucson AZ 85724 USA.
Adv Sci (Weinh). 2018 Sep 27;5(11):1800447. doi: 10.1002/advs.201800447. eCollection 2018 Nov.
Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists. Here, a new one-step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody-drug conjugates (ADCs) on the surface of immune cells is presented. Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells. The embedding of hydrophobized ADCs on the immune cell membrane using the strategy in this study provides noninvasive, nontoxic, and homogenous modifications that transiently arm immune cells with highly potent cytotoxic drugs targeted toward cancer cells. The resulting surface-engineered immune cells with ADCs significantly suppress the tumor growth and drive the eradication of target cancer cells through combinatorial anticancer effects. This novel strategy allows convenient and timely preparation of advanced chemoimmunotherapy on a single immune cell to treat various types of cancer.
传统的联合抗癌疗法已显示出有前景的结果;然而,人们仍对开发新方法以加强并可能融合化疗和免疫疗法有着浓厚兴趣。在此,提出了一种新的一步法,通过在免疫细胞表面自发且快速地掺入疏水化抗体-药物偶联物(ADC),将免疫细胞立即转变为靶向形式的化学免疫疗法。该方法的治疗目标包括靶向递送强效化疗药物以避免不良反应、增强输注的免疫细胞向肿瘤部位的迁移,以及保持免疫细胞对肿瘤细胞的强烈细胞毒活性。利用本研究中的策略将疏水化ADC嵌入免疫细胞膜,可提供无创、无毒且均匀的修饰,使免疫细胞短暂地配备针对癌细胞的高效细胞毒药物。所得的带有ADC的表面工程化免疫细胞通过联合抗癌作用显著抑制肿瘤生长并促使靶癌细胞被清除。这种新策略允许在单个免疫细胞上方便且及时地制备先进的化学免疫疗法,以治疗各种类型的癌症。