Doxorubicin plus interleukin-2 chemoimmunotherapy against breast cancer in mice
Doxorubicin plus interleukin-2 chemoimmunotherapy against breast cancer in mice
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DOI：
10.1158/0008-5472.can-05-3963
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发表时间：
2006-05-15
期刊：
影响因子：
11.2
通讯作者：
Ehrke, M. Jane
中科院分区：
文献类型：
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作者：
Ewens, Andrew;Luo, Liqun;Ehrke, M. Jane
正如最近所描述的那样，在S.C. E0771肿瘤植入同系C57BL/6小鼠后，局部侵入真皮层和腹膜，转移至肺，并在宿主中诱导非特异性免疫抑制。使用该乳腺髓腺癌模型，检查了由单次中等剂量的多柔比星随后每日两次中等剂量的白细胞介素-2持续30天组成的疗法在给予患有已确定疾病的动物时的功效和作用机制。这种组合治疗，而不是单独的组合物，导致40%的小鼠无肿瘤长期存活，没有显著的毒性，83%的存活者具有对E0771细胞特异性的免疫记忆。治疗还降低了E0771肿瘤诱导的免疫抑制。对治疗的完全应答需要功能性CD8（+）T细胞，而自然杀伤细胞的耗竭仅导致应答率降低。通过基于核磁共振的代谢组学分析鉴定了与治疗反应相关且似乎可预测治疗反应的血清"生物标志物"谱。这种无毒治疗的疗效和能够预测哪个个体对治疗有反应的潜力是使这种化学免疫疗法对临床测试有吸引力的特征。
As recently characterized, following s.c. implantation into syngeneic C57BL/6 mice, E0771 tumor invades locally into dermal layers and peritoneum, metastasizes to the lung, and induces a nonspecific immunosuppression in the host. Using this breast medullar adenocarcinoma model, a therapy consisting of a single moderate dose of doxorubicin followed by twice daily moderate doses of interleukin-2 for 30 days was examined for efficacy and mechanism of action when given to animals with established disease. This combination treatment, but not combinants alone, resulted in tumor-free long-term survival of 40% of the mice without significant toxicity and 83% of survivors had immune memory specific for E0771 cells. Treatment also decreased immune suppression induced by E0771 tumor. Full response to treatment required functional CD8(+) T cells, whereas depletion of natural killer cells caused only a reduction in response rate. A serum "biomarker" profile that correlated with, and seemed predictive of, response to treatment was identified by nuclear magnetic resonance-based metabonomic analysis. The efficacy of this nontoxic treatment and the potential to be able to predict which individual is responding to treatment are characteristics that make this chemoimmunotherapy attractive for clinical testing.