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犬活化 T 细胞和细胞因子诱导的杀伤细胞在体外对犬恶性黑色素瘤的抗肿瘤活性

英文原题:Anti-tumour activity of canine activated T-cells and cytokine-induced killer cells against canine malignant melanoma in vitro.

查看英文原题

Anti-tumour activity of canine activated T-cells and cytokine-induced killer cells against canine malignant melanoma in vitro.

PubMed 2026/07/29(内容时间) Vet J Q1 · IF 2.7(JCR 2025)

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中文摘要

过继性细胞转移(ACT)免疫治疗是一种有前景的癌症治疗方法,利用体外扩增的免疫效应细胞,如T淋巴细胞、自然杀伤(NK)细胞和细胞因子诱导的杀伤(CIK)细胞。CIK细胞具有T细胞和NK细胞样双重特性,表现出高增殖能力、细胞溶解活性和非MHC限制性肿瘤识别。犬恶性黑色素瘤(CMM)是一种侵袭性肿瘤,与人类黑色素瘤具有重要的转化相关性,但CIK细胞对CMM的细胞毒性潜力尚未被探索。

本研究旨在从健康供体中扩增并功能性表征犬CIK细胞和T细胞,比较它们在异体和自体条件下对CMM细胞系的细胞毒性活性。分离外周血单核细胞,并使用标准化方案进行扩增,包括IFN-、抗CD3/CD28激活和IL-2补充。流式细胞术确认成功扩增,CIK细胞显示85% NKp46表达,T细胞达到91.96% CD8表达,扩增倍数相当(7.94 vs. 7.88)。针对七种CMM细胞系的细胞毒性试验显示,两种效应细胞群均具有强大的抗肿瘤活性,在10:1效应细胞与靶细胞比例下,异体试验中CIK细胞平均杀伤率为61.5%,T细胞为59.8%。Pearson相关分析显示,效应细胞数量与靶细胞活力呈强负相关(CIK细胞r = -0.960;T细胞r = -0.790)。细胞因子谱分析显示不同的分泌模式,T细胞产生更广泛的细胞因子 repertoire。这些发现确立了CIK细胞和T细胞对CMM的可行性和相当疗效,支持其用于犬黑色素瘤免疫治疗的治疗开发。

展开英文摘要原文

Adoptive cell transfer (ACT) immunotherapy represents a promising therapeutic approach for cancer treatment, utilising ex vivo-expanded immune effector cells such as T-lymphocytes, natural killer (NK) cells, and cytokine-induced killer (CIK) cells.

CIK cells are characterised by dual T-cell and NK cell-like properties, exhibiting high proliferative capacity, cytolytic activity, and non-MHC-restricted tumour recognition. Canine malignant melanoma (CMM) is an aggressive neoplasm with significant translational relevance to human melanoma, yet the cytotoxic potential of CIK cells against CMM remains unexplored.

This study aimed to expand and functionally characterise canine CIK and T-cells from healthy donors, comparing their cytotoxic activity against CMM cell lines in allogeneic and autologous settings. Peripheral blood mononuclear cells were isolated and expanded using standardised protocols with IFN- , anti-CD3/CD28 activation, and IL-2 supplementation. Flow cytometry confirmed successful expansion with CIK cells showing 85% NKp46 expression and T-cells reaching 91. 96% CD8 expression, with comparable expansion folds (7. 94 vs.

7. 88). Cytotoxicity assays against seven CMM cell lines demonstrated robust anti-tumour activity for both effector populations, with CIK cells achieving 61. 5% mean killing and T-cells 59. 8% in allogeneic assays at 10:1 effector-to-target ratios. Pearson's correlation analysis revealed strong negative correlations between effector cell numbers and target viability (r = -0. 960 for CIK cells; r = -0. 790 for T cells). Cytokine profiling showed distinct secretion patterns, with T-cells producing a broader cytokine repertoire.

These findings establish the feasibility and comparable efficacy of both CIK cells and T-cells against CMM, supporting their therapeutic development for canine melanoma immunotherapy.

论文信息

作者
Conti LC、Capellero S、Piras L、Morello E、Iurascu S、Erriquez J、Marconato L、Aresu L
单位
Department of Veterinary Sciences, University of Turin, Grugliasco, TO, Italy; Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: luiza.cesarconti@unito.it.Italy
期刊
Veterinary journal (London, England : 1997)2026 Oct
原文标识
PubMed 42526683 · DOI 10.1016/j.tvjl.2026.106787