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用抗犬PD-1治疗性抗体治疗的4期口腔恶性黑色素瘤犬的长期存活:一例随访病例报告

Long-term survival of dogs with stage 4 oral malignant melanoma treated with anti-canine PD-1 therapeutic antibody: A follow-up case report.

作者信息

Igase Masaya, Inanaga Sakuya, Tani Kenji, Nakaichi Munekazu, Sakai Yusuke, Sakurai Masashi, Kato Masahiro, Tsukui Toshihiro, Mizuno Takuya

机构信息

Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.

Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.

出版信息

Vet Comp Oncol. 2022 Dec;20(4):901-905. doi: 10.1111/vco.12829. Epub 2022 May 17.

Abstract

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.

摘要

一种靶向程序性细胞死亡蛋白1(PD-1)的单克隆抗体是治疗人类癌症最有前景的疗法之一。人体临床研究表明,抗PD-1抗体可产生持久的肿瘤反应。此前,我们制备了一种抗犬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,在初步研究发表时,仍有两例OMM病例正在接受治疗。在此,我们描述这两例病例的长期随访情况。尽管两例病例均显示长期存活且完全缓解(CR),但肿瘤反应有所不同;其中一例起效缓慢,另一例即使在停药后仍观察到持久反应。两例病例在治疗期间均发生了继发性恶性肿瘤。这项随访研究表明,ca-4F12-E6可使犬的CR维持超过1年。此外,与传统疗法相比,肿瘤反应模式独特。这些结果表明,兽医学免疫疗法可能需要新的肿瘤反应评估标准。无论短期治疗反应如何,长期随访都是必要的。

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