Clinical efficacy of anti-programmed death ligand 1 antibody HFC-L1/c4G12 in dogs with malignant tumors: an exploratory study.

IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES
Satoshi Takagi, Michihito Tagawa, Naoya Maekawa, Satoru Konnai, Yumiko Kagawa, Kenji Hosoya, Akinori Yamauchi, Ayano Kudo, Shintaro Kamo, Sangho Kim, Ryohei Kinoshita, Tatsuya Deguchi, Ryo Owaki, Yurika Tachibana, Madoka Yokokawa, Hiroto Takeuchi, Hayato Nakamura, Yukinari Kato, Shigeki Kanazawa, Tomoyuki Abe, Takuya Furuta, Keiichi Yamamoto, Yasuhiko Suzuki, Tomohiro Okagawa, Shiro Murata, Kazuhiko Ohashi
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Abstract

Cancer in dogs remains a major challenge in modern veterinary medicine. Immunotherapy using immune checkpoint inhibitors (ICIs) is available for various human tumor types, and recent veterinary clinical studies have shown that ICIs are a promising approach for treating canine cancers. A canine chimeric anti-PD-L1 antibody, c4G12 (HFC-L1), has been investigated for canine cancer immunotherapy; however, its clinical benefits have not been well characterized in tumors other than pulmonary metastatic (stage IV) oral malignant melanoma (OMM). To explore the efficacy and safety of HFC-L1, we conducted a clinical study in dogs with stage I-III OMM or other tumor types (n=12). HFC-L1 treatment at a dose of 5 mg/kg every 2 weeks was well tolerated, and no grade 3 or higher treatment-related adverse events were reported. Among the dogs eligible for response evaluation (n=10), a partial response was observed in one dog with squamous cell carcinoma, resulting in an objective response rate of 10%. In addition, in a dog with ceruminous cell carcinoma, clinical evidence of a tumor response was observed in metastatic lung lesions. Together, these results suggest that the HFC-L1 therapy is applicable for the treatment of various tumor types, although its clinical benefits should be further evaluated in clinical studies involving a larger number of dogs with each tumor type.

抗程序性死亡配体1抗体HFC-L1/c4G12对犬恶性肿瘤临床疗效的探索性研究
狗的癌症仍然是现代兽医的一个主要挑战。使用免疫检查点抑制剂(ICIs)的免疫疗法可用于各种人类肿瘤类型,最近的兽医临床研究表明,ICIs是治疗犬癌症的一种很有前途的方法。犬嵌合抗pd - l1抗体c4G12 (HFC-L1)已被研究用于犬癌症的免疫治疗;然而,除肺转移性(IV期)口腔恶性黑色素瘤(OMM)外,其临床疗效尚未得到很好的表征。为了探索HFC-L1的有效性和安全性,我们在I-III期OMM或其他肿瘤类型的狗(n=12)中进行了临床研究。每2周5mg /kg剂量的HFC-L1治疗耐受性良好,没有3级或更高级别治疗相关不良事件的报道。在符合反应评估条件的狗(n=10)中,有一只患有鳞状细胞癌的狗观察到部分反应,客观反应率为10%。此外,在一只患有耵聍细胞癌的狗中,在转移性肺病变中观察到肿瘤反应的临床证据。综上所述,这些结果表明HFC-L1疗法适用于治疗各种类型的肿瘤,尽管其临床疗效有待于在涉及更多犬类肿瘤类型的临床研究中进一步评估。
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来源期刊
Journal of Veterinary Medical Science
Journal of Veterinary Medical Science 农林科学-兽医学
CiteScore
2.30
自引率
8.30%
发文量
230
审稿时长
9-18 weeks
期刊介绍: JVMS is a peer-reviewed journal and publishes a variety of papers on veterinary science from basic research to applied science and clinical research. JVMS is published monthly and consists of twelve issues per year. Papers are from the areas of anatomy, physiology, pharmacology, toxicology, pathology, immunology, microbiology, virology, parasitology, internal medicine, surgery, clinical pathology, theriogenology, avian disease, public health, ethology, and laboratory animal science. Although JVMS has played a role in publishing the scientific achievements of Japanese researchers and clinicians for many years, it now also accepts papers submitted from all over the world.
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