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评估重组犬白细胞介素-15 治疗对癌症犬的临床和免疫学反应:一项初步研究

英文原题:Evaluation of clinical and immunological responses to recombinant canine interleukin-15 therapy in dogs with cancer: A pilot study.

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Evaluation of clinical and immunological responses to recombinant canine interleukin-15 therapy in dogs with cancer: A pilot study.

PubMed 2025/03/27(内容时间) Vet Immunol Immunopathol Q2 · IF 1.8(JCR 2025)

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中文摘要

白细胞介素-15(IL-15)是一种多效性细胞因子,在固有免疫和适应性免疫中发挥关键作用。因此,它是一种有前景的癌症治疗药物。尽管人们对使用IL-15作为免疫治疗药物的兴趣日益增长,但关于其在犬类癌症中的免疫学和临床效应的报道非常少。

在本研究中,我们制备了重组犬IL-15(rcIL-15),并在15只患有不同类型肿瘤的犬中评估了其与节拍式环磷酰胺联合使用的临床和免疫调节效应。治疗结果在一项前瞻性临床试验中进行评估。低剂量环磷酰胺(12.5 mg/m 2,PO,SID)连续给药8周。从第14天开始,在给予环磷酰胺后,rcIL-15(20 μg/kg每日)静脉注射8天。联合治疗的最佳疾病控制率为66.6 %,其中最显著的PR占血液系统恶性肿瘤的33.3 %。不良事件极少,主要为1级严重程度。

此外,rcIL-15给药导致抗癌淋巴细胞亚群显著升高,如NK 细胞和细胞毒性T细胞,同时Ki-67表达增加,表明细胞增殖。这些变化与临床结局改善相关。

我们的发现强调了rcIL-15与节拍式环磷酰胺联合治疗多种犬类癌症的治疗潜力和安全性。

展开英文摘要原文

Interleukin-15 (IL-15) is a pleiotropic cytokine that plays a pivotal role in innate and adaptive immunity.

Therefore, it is a promising therapeutic agent for cancer treatment. Despite growing interest in the use of IL-15 as an immunotherapeutic agent, there have been very few reports on its immunological and clinical effects in canine cancers. In this study, we generated recombinant canine IL-15 (rcIL-15) and evaluated its clinical and immunomodulatory effects in combination with metronomic cyclophosphamide in 15 canines with various tumor types.

The treatment outcomes were assessed in a prospective clinical trial. Low-dose cyclophosphamide (12. 5 mg/m 2 , PO, SID) was continuously administered for 8 weeks. Starting on day 14, after administering cyclophosphamide, rcIL-15 (20 μg/kg daily) was injected intravenously for 8 days. The disease control rate for combination therapy was 66. 6 %, with the most notable partial response accounting for 33. 3 % of hematological malignancies. The adverse events were minimal and primarily of grade 1 severity.

Moreover, rcIL-15 administration led to significant elevations in anticancer lymphocyte subsets, such as natural killer and cytotoxic T cells, along with increased Ki-67 expression, indicating cellular proliferation. These changes were correlated with improved clinical outcomes.

Our findings underscore the therapeutic potential and safety of combining rcIL-15 and metronomic cyclophosphamide for the treatment of various canine cancers.

论文信息

作者
Lim YJ、Lim MS、Lee JJ、Bae H、Baek YJ、Kim GS、An Y、Kim SK
第一作者单位
Department of Integrated Life Science and Technology, Kongju National University, Yesan-gun, Chungnam, Republic of Korea; Department of Companion and Laboratory Animal Science, College of Industrial Science, Kongju National University, Yesan-gun, Chungnam, Republic of Korea. Electronic address: luj9511@naver.com.South Korea
通讯作者单位
College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: yudh@gnu.ac.kr.South Korea
期刊
Veterinary immunology and immunopathology2025 May
原文标识
PubMed 40203669 · DOI 10.1016/j.vetimm.2025.110923