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:Immunotherapeutic allogeneic dendritic cell and autologous tumor cell fusion vaccine alone or combined with radiotherapy in canine oral malignant melanoma is safe and potentially effective.
Immunotherapeutic allogeneic dendritic cell and autologous tumor cell fusion vaccine alone or combined with radiotherapy in canine oral malignant melanoma is safe and potentially effective.
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该手稿证明了树突状细胞/肿瘤细胞融合疫苗免疫治疗单独或联合放疗的安全性。结果支持进一步扩大这种免疫治疗、修改联合治疗方案和方案,以及研究将 DC 疫苗与其他治疗方式联合使用。
免疫疗法是癌症治疗中一个有前景的突破,目前正在犬黑色素瘤中进行探索。树突状细胞(DCs)通过抗原呈递功能在启动T细胞介导的免疫反应中发挥关键作用。将免疫疗法与放射疗法相结合,可能通过免疫调节产生更显著的抗癌疗效。
我们的研究报告了一种免疫疗法——同种异体树突状细胞与自体肿瘤细胞融合疫苗——单独或联合大分割放射治疗在犬口腔恶性黑色素瘤中的安全性和疗效的初步结果。
招募了两组经组织病理学诊断为口腔恶性黑色素瘤的犬。第1组(DCRT)犬接受DC融合疫苗联合放疗。第2组(DC)犬仅接受DC融合疫苗。DC疫苗接种每2周一次,共4剂。放疗每周进行,共5次分割。回顾性收集接受卡铂治疗的犬作为对照组(第3组)。
第1组纳入5只犬(2只II期,3只III期),第2组纳入11只(3只I/II期,8只III/IV期),对照组纳入8只(2只I/II期,6只III/IV期)。DC和DCRT均耐受良好,仅报告了轻度不良事件,包括黏膜炎、胃肠道不适和注射部位反应。第1、2、3组的中位无进展间期分别为214天(95% CI,NA,因数据不足)、100天(95% CI,27-237)和42天(95% CI,NA-170),差异无统计学意义。第1、2、3组的1年生存率分别为20%、54.5%和12.5%。DCRT组犬在整个治疗过程中表现出显著高于DC组的TGF-β信号,提示可能存在更高程度的免疫抑制。
Our research reported a preliminary result of the safety and outcome of a kind of immunotherapy, the allogeneic dendritic cell and autologous tumor cell fusion vaccine, alone or in combination with hypofractionated radiation therapy, in canine oral malignant melanoma.
Two groups of dogs with histopathological diagnoses of oral malignant melanoma were recruited. In group 1 (DCRT), dogs received a combination of DC fusion vaccine and radiotherapy. In group 2 (DC), dogs received DC fusion vaccine alone. DC vaccination was given once every 2 weeks for four doses. Radiotherapy was performed weekly for five fractions. Dogs that received carboplatin were retrospectively collected as a control group (group 3).
Five dogs were included in group 1 (two stage II, three stage III), 11 in group 2 (three stage I/II, eight stage III/IV), and eight (two stage I/II, six stage III/IV) in the control group. Both DC and DCRT were well-tolerated, with only mild adverse events reported, including mucositis, gastrointestinal discomfort, and injection site reactions. The median progression-free intervals in groups 1, 2, and 3 were 214 (95% CI, NA, due to insufficient data), 100 (95% CI, 27-237), and 42 days (95% CI, NA-170), respectively, which were not significantly different. The 1-year survival rates were 20, 54.5, and 12.5% in groups 1, 2, and 3. Dogs in the DCRT group exhibited significantly higher TGF-β signals than the DC group throughout the treatment course, indicating a possible higher degree of immunosuppression.
The manuscript demonstrated the safety of dendritic cell/tumor cell fusion vaccine immunotherapy, alone or in combination with radiotherapy. The results support further expansion of this immunotherapy, modification of combination treatment and protocols, and investigation of combining DC vaccine with other treatment modalities. CLINICAL TRIAL REGISTRATION: Preclinical Trials, PCTE0000475.
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