The B-cell coreceptor, CD19 is a transmembrane protein expressed throughout B-cell ontogeny from pro-B cell to plasmablast. It plays an important role in B-cell development and function and is an attractive target for antibody-directed immunotherapies against B-cell malignancies, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (B-NHL) in humans. With the rapid development of next-generation immunotherapies aimed at improving therapeutic efficacy, there is a pressing need for a clinically relevant, immune-competent, spontaneous animal model to derisk these new approaches and inform human immunotherapy clinical trials. Pet dogs develop spontaneous B-cell malignancies, including B-NHL and leukemias that share comparable oncogenic pathways and similar immunosuppressive features to human B-cell malignancies. Despite treatment with multiagent chemotherapy, durable remissions in canine B-NHL are rare and most dogs succumb to their disease within 1 year of diagnosis. Here we report the development and validation of an anti-canine CD19-targeting monoclonal antibody and its single-chain derivatives, which enable next-generation CD19-targeted immunotherapies to be developed and evaluated in client-owned dogs with spontaneous B-NHL. These future in vivo studies aim to provide important information regarding the safety and therapeutic efficacy of CD19-targeted mono- and combination therapies and identify correlative biomarkers of response that will help to inform human clinical trial design. In addition, development of canine CD19-targeted immunotherapies aims to provide better therapeutic options for pet dogs diagnosed with B-cell malignancies.

中文翻译：

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用于诊断和未来治疗目的的犬 CD19 抗体的生成和验证。

B 细胞辅助受体 CD19 是一种跨膜蛋白，在从前 B 细胞到浆母细胞的整个 B 细胞个体发育过程中表达。它在 B 细胞发育和功能中起着重要作用，并且是针对 B 细胞恶性肿瘤的抗体导向免疫疗法的一个有吸引力的目标，包括急性淋巴细胞白血病 (ALL)、慢性淋巴细胞白血病 (CLL) 和非霍奇金淋巴瘤 (B -NHL）在人类中。随着旨在提高治疗效果的下一代免疫疗法的快速发展，迫切需要一种临床相关的、具有免疫能力的、自发的动物模型，以消除这些新方法的风险并为人类免疫疗法临床试验提供信息。宠物狗患上自发性 B 细胞恶性肿瘤，包括 B-NHL 和白血病，它们与人类 B 细胞恶性肿瘤具有相似的致癌途径和相似的免疫抑制特征。尽管使用多药化疗进行治疗，但犬 B-NHL 的持久缓解很少见，大多数狗在诊断后 1 年内死于疾病。在这里，我们报告了抗犬 CD19 靶向单克隆抗体及其单链衍生物的开发和验证，这使得下一代 CD19 靶向免疫疗法能够在患有自发性 B-NHL 的客户拥有的狗中开发和评估。这些未来的体内研究旨在提供有关 CD19 靶向单一疗法和联合疗法的安全性和治疗功效的重要信息，并确定有助于为人类临床试验设计提供信息的相关反应生物标志物。此外，