Cytokine immunotherapy of cancer with controlled release biodegradable microspheres in a human tumor xenograft SCID mouse model

Cytokine immunotherapy of cancer with controlled release biodegradable microspheres in a human tumor xenograft SCID mouse model
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DOI:
10.1007/s002620050455
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发表时间:
1998-03-01
影响因子:
5.8
通讯作者:
Bankert, RB
Bankert, RB
中科院分区:
医学3区
文献类型:
--
作者:
Egilmez, NK;Jong, YS;Bankert, RB

文献摘要

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评价了一种新型可生物降解的聚乳酸微球制剂在人肿瘤移植瘤/严重联合免疫缺陷(SCID)小鼠模型中的细胞因子免疫治疗作用。将白介素2(IL-2)载瘤微球与肿瘤细胞共同注射到皮下,可完全抑制80%的动物移植瘤。相比之下,牛血清白蛋白(BSA)颗粒或聚乙二醇/IL-2团注在阻止肿瘤生长方面无效。微球释放的IL-2的抗肿瘤作用是由小鼠自然杀伤细胞介导的。这是第一个证据表明,从可生物降解的微球持续体内输送IL-2可以引发对人类肿瘤异种移植的排斥反应。使用聚乳酸微球将细胞因子输送到肿瘤环境中,可以为癌症的基因治疗提供一种更安全和更简单的替代方案。
A novel biodegradable poly(lactic acid) microsphere formulation was evaluated for in vivo cytokine immunotherapy of cancer in a human tumor xenograft/severe combined immunodeficiency (SCID) mouse model. Co-injection of interleukin-2 (IL-2)-loaded microspheres with tumor cells into a subcutaneous site resulted in the complete suppression of tumor engraftment in 80% of animals. In contrast, bovine-serum-albumin(BSA)-loaded particles or bolus injections of poly(ethylene glycol)/IL-2 were ineffective in preventing tumor growth. The antitumor effect of IL-2 released by the microspheres was shown to be mediated by the mouse natural killer cells. This is the first evidence that the rejection of human tumor xenografts can be provoked by the sustained in vivo delivery of IL-2 from biodegradable microspheres. The use of poly(lactic acid) microspheres to deliver cytokines to the tumor environment could provide a safer and simpler alternative to gene therapy protocols in the treatment of cancer.