基于三维光声成像抗人sAPRIL中和抗体抑制乳腺癌的实验研究

As A Proliferation-inducting ligand (APRIL) has closely relation with a wide variety of tumor cells proliferation, survival and acceleration of tumor formation, it became a new target for cancer treatment. To study the inhibition effect of breast cancer cells in vivo, based on our former achievements in anti-human soluble APRIL (sAPRIL) neutralization antibodies that can inhibit the sAPRIL promote breast cancer cells proliferation. Combined with our preliminary studies in photoacoustic imaging technology, building breast cancer model in the mice, using Arc shape dot matrix PA signal collection technology to improve the space resolution of the imaging device, we can construct new tumor blood vessels in real-time 3D photoacoustic imaging and analyze the relation between breast cancer 3D photoacoustic imaging and pathology. Then we evaluate therapeutic effect of anti-human sAPRIL antibodies which inhibit the sAPRIL to promote breast cancer cells proliferation in situ and tumor growth, transfermation in vivo. Our puepose is to develop high resolution 3D photoacoustic imaging device, to establish methods of diagnosis of breast cancer and therapeutic effect evaluation of breast cancer in vivo, then to explore the inhibition effect of anti-human sAPRIL neutralization antibodies in APRIL the high expression breast cancer treatment, and finally to provide analysis and detection methods for related cancer therapy.

增殖诱导配体(A Proliferation-inducting ligand, APRIL)因与多种肿瘤细胞增殖和存活以及加速肿瘤形成等密切相关而成为肿瘤治疗的新靶点，为深入探讨其体内抑制乳腺癌细胞的作用，本项目在已成功获得具有抑制sAPRIL促乳腺癌细胞增殖作用的抗人sAPRIL中和抗体基础上，结合我们前期在光声成像技术方面的研究，构建裸鼠荷乳腺癌肿瘤模型，运用弧状点阵光声信号采集技术构建高分辨率的光声成像系统，重建肿瘤新生血管的光声三维断层图像，分析乳腺癌光声三维图像与病理检验的相关性，在体原位评价抗人sAPRIL中和抗体在裸鼠体内抑制肿瘤形成和在荷瘤裸鼠体内抑制肿瘤生长的疗效。旨在优化高分辨率的三维光声成像装置；建立基于光声成像的乳腺肿瘤诊断、评价方法；研究抗人sAPRIL中和抗体在体治疗APRIL高表达乳腺癌的疗效；为相关的肿瘤研究提供新的分析检测方法。

肿瘤精准诊疗迫切需要提供个性化安全有效的制剂和科学有效的评价方法，增殖诱导配体(A Proliferation-inducting ligand, APRIL)因与多种肿瘤细胞增殖和存活以及加速肿瘤形成等密切相关而成为肿瘤治疗的新靶点，因为肿瘤血管新生是评价肿瘤生长转移以及疗效评估的重要指标，而三维光声断层成像所表现的是生物组织内的光学信息，可以对肿瘤组织进行精确的功能成像。本项目主要研究内容是优化构建高分辨率的三维光声成像装置；建立基于光声成像的乳腺肿瘤诊断、评价方法；研究抗人sAPRIL中和抗体在体治疗APRIL高表达乳腺癌的疗效，为相关肿瘤精准诊疗研究提供一种在体原位实时有效的影像学分析检测方法。通过本研究，我们制备了抗人sAPRIL中和抗体，在体外证实该抗体具有抑制乳腺癌细胞增殖作用，在体内证明抗人sAPRIL中和抗体能抑制裸鼠体内肿瘤形成和肿瘤生长，研究中发现阻断增殖诱导配体的生物学活性，可以完全抑制肿瘤细胞增殖、缩短肿瘤细胞寿命以及减缓肿瘤形成，通过抗人sAPRIL中和抗体治疗乳腺癌动物模型实验，筛选优化了抗人sAPRIL中和抗体抑制乳腺癌肿瘤的方案，建立了基于高对比度高分辨率三维光声成像技术的实体肿瘤生物治疗在体动态监测评价的技术方法，开发了光声成像数据采集和控制软件，设计并开发了一套三维光声断层成像系统，通过裸鼠乳腺癌血管三维成像与组织病理学检测结果的对比，证实该系统可以对实体肿瘤组织进行高分辨率、高灵敏度、实时快速的肿瘤成像检测，完全能够实现在体实时动态的评价肿瘤治疗效果。该套三维光声断层成像系统的推广应用，为抗体抑制高表达某种抗原肿瘤的治疗药物的筛选和治疗效果的评估等分子影像学研究提供了一种新的技术方法。