对于改进转移融合驱动的肺泡横纹肌肉瘤的免疫治疗,ErbB2(HER2)-CAR-NK-92细胞是一种很有效的选择。
ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma.
发表日期:2023
作者:
Catrin Heim, Laura M Moser, Herman Kreyenberg, Halvard B Bonig, Torsten Tonn, Winfried S Wels, Elise Gradhand, Evelyn Ullrich, Michael T Meister, Marian Groot Koerkamp, Frank C P Holstege, Jarno Drost, Jan-Henning Klusmann, Peter Bader, Michael Merker, Eva Rettinger
来源:
Experimental Hematology & Oncology
摘要:
转移性横纹肌肉瘤(RMS)是一个具有挑战性的肿瘤实体,逃避了传统治疗和内源性抗肿瘤免疫反应,突显了新型治疗策略的需求。应用嵌合抗原受体(CAR)技术于自然杀伤(NK)细胞可能提供安全、有效且经济的治疗方法,增强癌症免疫监视。本研究评估了在体外和转移性异种移植小鼠模型中,临床可应用的CAR工程化NK细胞株NK-92/5.28.z对ErbB2阳性RMS的疗效。结果显示,NK-92/5.28.z细胞有效杀伤体外RMS细胞,并显著延长小鼠的生存时间及抑制肿瘤进展。NK-92/5.28.z细胞在肿瘤部位的持久存在,表明有效的抗肿瘤反应,这有助于克服当前固体肿瘤治疗中的障碍。这些发现鼓励进一步开发NK-92/5.28.z细胞作为现成的用于治疗转移性RMS的免疫疗法。版权所有 © 2023 Heim, Moser, Kreyenberg, Bonig, Tonn, Wels, Gradhand, Ullrich, Meister, Koerkamp, Holstege, Drost, Klusmann, Bader, Merker and Rettinger.
Metastatic rhabdomyosarcoma (RMS) is a challenging tumor entity that evades conventional treatments and endogenous antitumor immune responses, highlighting the need for novel therapeutic strategies. Applying chimeric antigen receptor (CAR) technology to natural killer (NK) cells may offer safe, effective, and affordable therapies that enhance cancer immune surveillance.Here, we assess the efficacy of clinically usable CAR-engineered NK cell line NK-92/5.28.z against ErbB2-positive RMS in vitro and in a metastatic xenograft mouse model.Our results show that NK-92/5.28.z cells effectively kill RMS cells in vitro and significantly prolong survival and inhibit tumor progression in mice. The persistence of NK-92/5.28.z cells at tumor sites demonstrates efficient antitumor response, which could help overcome current obstacles in the treatment of solid tumors.These findings encourage further development of NK-92/5.28.z cells as off-the-shelf immunotherapy for the treatment of metastatic RMS.Copyright © 2023 Heim, Moser, Kreyenberg, Bonig, Tonn, Wels, Gradhand, Ullrich, Meister, Koerkamp, Holstege, Drost, Klusmann, Bader, Merker and Rettinger.