肿瘤内注射 IL2 和 TNF 融合蛋白可治愈癌症而不产生保护性免疫。
Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer without establishing protective immunity.
机构信息
Department of Chemistry & Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, (ETH Zürich), Vladimir-Prelog-Weg 1-5/10, CH-8093 Zürich, Switzerland.
Philochem AG, Libernstrasse 3, CH-8112 Otelfingen, Switzerland.
出版信息
Immunotherapy. 2018 Mar;10(3):177-188. doi: 10.2217/imt-2017-0119.
Abstract
AIM
The combination of tumor-targeting IL2- and TNF-based antibody-cytokine fusions has exhibited encouraging results in mouse and men. Here, we studied their combination to assess efficacy and mechanism of action in four different immunocompetent mouse models of cancer.
METHODS
Mice receiving a single intratumoral injection of F8-IL2, F8-TNF or the combination were investigated for tumor-infiltrating leukocytes and rechallenged when cured.
RESULTS
In three models, a proportion of treated animals could be cured, most probably by infiltrating NK and CD8 T cells. Most of the cured mice did not acquire protective immunity when rechallenged with the same tumor cell line.
CONCLUSION
Immunocompetent mouse tumor models may not be adequate enough to predict the search for more efficacious therapy regimens.
摘要
目的
肿瘤靶向 IL2 和 TNF 双功能抗体融合细胞因子在小鼠和人类中表现出了令人鼓舞的结果。在这里，我们研究了它们在四种不同的免疫活性的小鼠癌症模型中的联合应用，以评估其疗效和作用机制。
方法
对接受 F8-IL2、F8-TNF 或联合治疗的小鼠进行肿瘤浸润白细胞的检测，并在治愈后进行重新攻击。
结果
在三种模型中，一部分治疗后的动物可以被治愈，这很可能是通过浸润的 NK 和 CD8 T 细胞。大多数治愈的小鼠在重新用相同的肿瘤细胞系攻击时没有获得保护性免疫。
结论
免疫活性的小鼠肿瘤模型可能不足以预测更有效的治疗方案的研究。
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