Long-term survival of dogs with stage 4 oral malignant melanoma treated with anti-canine PD-1 therapeutic antibody: A follow-up case report
Long-term survival of dogs with stage 4 oral malignant melanoma treated with anti-canine PD-1 therapeutic antibody: A follow-up case report
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DOI：
10.1111/vco.12829
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发表时间：
2022-05-17
影响因子：
2.1
通讯作者：
Mizuno, Takuya
中科院分区：
文献类型：
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作者：
Igase, Masaya;Inanaga, Sakuya;Mizuno, Takuya
针对程序性细胞死亡-1(PD-1)的单抗是治疗人类癌症最有前途的方法之一。对人类的临床研究表明，抗PD-1抗体提供了一种持久的肿瘤反应。此前，我们建立了一种抗犬PD-1治疗性抗体(ca-4F12-E6)，初步临床研究表明，该抗体对患有口腔恶性黑色素瘤(OMM)的犬有效。然而，当试点研究发表时，两个OMM病例仍在接受治疗。在这里，我们描述这两个病例的长期随访情况。虽然这两个病例都显示长期存活和完全缓解(CR)，但肿瘤反应不同；其中一例起效缓慢，第二例即使在停止治疗后也观察到持久的反应。两例患者在治疗过程中均发生继发性恶性肿瘤。这项跟踪研究显示，ca-4F12-E6在狗身上保持CR1年以上。此外，与传统疗法相比，肿瘤反应模式是独一无二的。这些结果表明，新的肿瘤反应评价标准可能是兽医免疫治疗所必需的。无论短期治疗反应如何，长期随访都是必要的。
A monoclonal antibody targeting programmed cell death-1 (PD-1) is one of the most promising treatments for human cancers. Clinical studies in humans demonstrated that the anti-PD-1 antibody provides a long-lasting tumour response. Previously, we established an anti-canine PD-1 therapeutic antibody (ca-4F12-E6), and the pilot clinical study demonstrated that the antibody was effective in dogs with oral malignant melanoma (OMM). However, two OMM cases were still undergoing treatment when the pilot study was published. Here, we describe the long-term follow-up of those two cases. Although both cases showed long-term survival with complete response (CR), the tumour response differed; the effect onset was slow in one case and a durable response was observed in the second case even after treatment discontinuation. Secondary malignant tumours occurred during treatment in both cases. This follow-up study revealed that ca-4F12-E6 maintains CR in dogs for more than 1 year. In addition, the pattern of tumour response was unique compared to conventional therapy. These results indicate that new evaluation criteria for tumour response may be necessary for immunotherapy in veterinary medicine. Long-term follow-up is necessary regardless of the short-term treatment responsiveness.