免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma.
Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma.
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过继性细胞治疗(ACT)已在几种人类和犬类癌症中进行了研究,并取得了一些有希望的临床结果,但尚未在犬口腔恶性黑色素瘤(OMM)中开展。
我们的手稿旨在探索一种ACT,即体外扩增的自体免疫细胞输注在犬OMM中的应用,因为这种肿瘤仍然是一个治疗难题。该研究招募了经组织病理学诊断为口腔恶性黑色素瘤的犬,制备其外周血单个核细胞,通过IL-15、IL-2和IL-21的刺激将其扩增为以非B非T细胞为主的细胞,然后将这些细胞回输到荷瘤犬体内。共纳入10只犬;3只犬未报告任何不良事件;3只出现轻度食欲改变;1只出现轻度肝指标升高,另外3只出现了不同程度的疑似过敏反应。中位无进展间期为49天。治疗期间出现疾病进展的犬生存期较短。这项初步研究表明该ACT疗效有限,并可能伴随不良事件。大多数招募的患者处于较晚期阶段且存在宏观病灶,这可能影响了治疗效果。在充分修改和标准化方案的前提下,进一步探索该细胞疗法在辅助治疗环境中的应用仍可考虑。
Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM).
Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumor-bearing dogs.
Ten dogs were enrolled; three dogs did not report any adverse events; three had a mildly altered appetite; one had a mildly increased liver index, while the other three developed suspected anaphylaxis at different levels. The median progression-free interval was 49 days. Dogs with progressive disease during treatment had a shorter survival. This pilot study indicates limited efficacy with potential adverse events of this ACT. Most recruited patients were in a later stage and had macroscopic disease, which might affect the treatment efficacy.
Further exploration of this cell therapy in an adjuvant setting, with adequate protocol modification and standardization, could still be considered.
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