Xia Yuan-Yuan, Liao Albert TaiChing, Liu Ru-Min, Yang Shu-Ya, Kuo Chien-Chun, Ke Chiao-Hsu, Lin Chen-Si, Lee Jih-Jong
Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Front Vet Sci. 2024 Aug 20;11:1397518. doi: 10.3389/fvets.2024.1397518. eCollection 2024.
Immunotherapy represents a promising breakthrough in cancer management and is being explored in canine melanomas. Dendritic cells (DCs) play a crucial role in priming T-cell-mediated immune reactions through the antigen-presenting function. Combining immunotherapy and radiation therapy may generate more substantial anti-cancer efficacy through immunomodulation.
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.
Preclinical Trials, PCTE0000475.
免疫疗法是癌症治疗领域一项颇具前景的突破，目前正应用于犬黑色素瘤的研究。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。免疫疗法与放射疗法相结合可能通过免疫调节产生更强的抗癌效果。
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低分割放射疗法治疗犬口腔恶性黑色素瘤的安全性和疗效的初步结果。
招募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）的犬接受DC融合疫苗与放射疗法联合治疗。第2组（DC）的犬仅接受DC融合疫苗治疗。DC疫苗每2周接种1次，共接种4剂。放射疗法每周进行1次，共5次。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只犬（3只I/II期，8只III/IV期），对照组纳入8只犬（2只I/II期，6只III/IV期）。DC和DCRT的耐受性均良好，仅报告了轻微不良事件，包括粘膜炎、胃肠道不适和注射部位反应。第1、2和3组的无进展生存期中位数分别为214天（95%CI，因数据不足未给出）、100天（95%CI，27 - 237）和42天（95%CI，未给出 - 170），差异无统计学意义。第1、2和3组的1年生存率分别为20%、54.5%和12.5%。在整个治疗过程中，DCRT组的犬TGF-β信号显著高于DC组，表明免疫抑制程度可能更高。
本研究证明了树突状细胞/肿瘤细胞融合疫苗免疫疗法单独或联合放射疗法的安全性。研究结果支持进一步扩大这种免疫疗法的应用范围，改进联合治疗方案，并研究DC疫苗与其他治疗方式的联合应用。
临床前试验，PCTE0000475。
