Development and validation of anti-canine reagents to enable pre-clinical development of novel therapeutics

抗犬试剂的开发和验证，以实现新型疗法的临床前开发

• 批准号: 10267452
• 负责人: XIAOMIN FAN
• 金额: $ 199.59万
• 依托单位: AVANTGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2022-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10267452
• 关键词: Affinity; Antibodies; Antigens; Biological Assay; Biological Markers; Biological Models; Cancer Patient; Canis familiaris; Development; Future; Immune response; Immunization; Immunotherapeutic agent; Lead; Lymphoma; Malignant Neoplasms; Monitor; Monoclonal Antibodies; Oryctolagus cuniculus; Outcome; Patients; Phase; Pilot Projects; Reagent; Safety; Therapeutic; Validation; Yeasts; anti-PD1 antibodies; antibody libraries; cancer immunotherapeutics; cell bank; chemotherapy; efficacy study; in vivo; mouse model; novel; novel therapeutics; pharmacokinetics and pharmacodynamics; preclinical development; programmed cell death protein 1; standard of care; success; treatment response

Dogs with naturally occurring cancers can serve as a better model system for evaluating novel cancer immuno-therapeutics than the traditional mouse model systems, and also provide a target patient group. However, use of canine cancer patients is currently limited by the availability of suitable reagents to monitor canine immune responses. The majority of commercially-available reagents for canine biomarkers are rabbit polyclonal reagents, which are not renewable and suffer from lot-lo-lot variability. Following their success in Phase I, here the company proposes to use their novel yeast rabbit antibody display platform to discover high affinity, highly specific rabbit monoclonal antibodies against an expanded panel of 26 canine biomarkers. In parallel, AvantGen plans to optimize the caninized anti-canine-PD-1 antibody isolated in Phase I as a canine immunotherapeutic, then perform a pilot study in pet dogs with lymphoma to assess its safety and efficacy as concurrent therapy with standard of care chemotherapy using the biomarker reagents generated during this project to assess in vivo immune responses to treatment. A successful outcome will result in a panel of high quality, well characterized, renewable reagents for canine biomarkers that will facilitate future development of immunotherapeutics plus provide a novel treatment for canine lymphoma.

与传统的小鼠模型系统相比，具有天然癌症的狗可以作为评估新型癌症免疫治疗药的更好模型系统，还提供目标患者组。但是，目前使用犬类癌患者的使用受到适当的试剂来监测犬免疫反应的限制。犬类生物标志物的大多数商业可用试剂都是兔多克隆试剂，这些试剂不可再生且遭受批量差异。在第一阶段的成功之后，该公司建议使用其新型的酵母兔抗体显示平台，以发现高亲和力，高度特异性的兔子单克隆抗体，以针对26个犬类生物标志物的扩展面板。同时，Avantgen计划优化在I期分离为犬类免疫治疗疗法的罐装抗甲氨酸-PD-1抗体，然后在患有淋巴瘤的PET Dogs中进行试验研究，以评估其安全性和效率作为同时治疗，并进行标准的护理化学治疗使用该项目中产生的生物标志物试剂来评估体内免疫反应对治疗。成功的结果将导致犬类生物标志物的高质量，表征良好的可再生试剂，这些试剂将促进免疫疗法的未来发育以及为犬淋巴瘤提供新颖的治疗方法。