MRl of prostate cancer antigen expression for diagnosis and immunotherapy.
MRl of prostate cancer antigen expression for diagnosis and immunotherapy.
复制标题
用于诊断和免疫治疗的前列腺癌抗原表达的MRl
DOI：
10.1371/journal.pone.0038350
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Ren J;Wang F;Wei G;Yang Y;Liu Y;Wei M;Huan Y;Larson AC;Zhang Z
肿瘤抗原（TA）靶向单克隆抗体（mAb）免疫疗法可有效治疗多种癌症病因；然而，这些方法在前列腺癌（PCa）患者的治疗中表现出不同的临床疗效。目前阻碍转化进展的一个障碍是无法量化到达肿瘤部位并与靶向TAs结合的单抗剂量。单抗与基于纳米粒子的磁共振成像（MRI）探针的耦合应该允许在体内测量患者特异性的生物分布；这些测量可以促进未来新型剂量学范式的发展，其中单抗剂量滴定以优化个体患者的结果。前列腺干细胞抗原（PSCA）广泛表达于前列腺癌（PCa）细胞表面。抗人PSCA单克隆抗体（mAb 7F5）结合到Au/Fe3O4 （GoldMag）纳米颗粒（mAb 7F5@GoldMag）上，作为PSCA特异性的诊断性MRI探针，可以可视化mAb在体内的生物分布。首先，评估了GoldMag颗粒的抗体固定化效率和psca特异性结合的有效性。接下来，给PC-3 （PSCA过表达的前列腺癌）和SMMC-7721（无PSCA表达的肝癌细胞）荷瘤小鼠注射mAb 7F5@GoldMag进行MRI。在注射后增加时间间隔评估MRI探针的生物分布；通过一系列肿瘤体积测量来评估治疗效果。通过光学图像和MRI验证mAb 7F5@GoldMag探针与PC-3细胞的靶向结合；SMMC-7721肿瘤未观察到选择性结合。与未处理的对照动物相比，mAb 7F5@GoldMag对PC-3荷瘤小鼠的免疫治疗效果得到证实，对肿瘤生长有显著抑制。我们有希望的结果表明，使用mAb 7F5@GoldMag探针作为PCa检测和免疫治疗的新范例是可行的。我们乐观地预计，这些方法有可能被转化为临床环境。
Tumor antigen (TA)–targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI) probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients. The prostate stem cell antigen (PSCA) is broadly expressed on the surface of prostate cancer (PCa) cells. Anti-human PSCA monoclonal antibodies (mAb 7F5) were bound to Au/Fe3O4 (GoldMag) nanoparticles (mAb 7F5@GoldMag) to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression) and SMMC-7721 (hepatoma cells without PSCA expression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements. Targeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals. Our promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a novel paradigm for the detection and immunotherapeutic treatment of PCa. We optimistically anticipate that the approaches have the potential to be translated into the clinical settings.
登录
查看更多内容
影响因子：
168.9
作者：
Grönberg, H
通讯作者：
Grönberg, H
DOI：
10.1158/1078-0432.ccr-09-2345
发表时间：
2010-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Campoli M;Ferris R;Ferrone S;Wang X
通讯作者：
Wang X
影响因子：
9.9
作者：
Mandal, M;Kundu, S;Pal, T
通讯作者：
Pal, T
影响因子：
6.7
作者：
Eyal, Erez;Bloch, B. Nicolas;Degani, Hadassa
通讯作者：
Degani, Hadassa
DOI：
10.1080/02652030600949592
发表时间：
2007-01-01
影响因子：
2.9
作者：
Li, Zhefei;Jian, Liru;Cui, Yali
通讯作者：
Cui, Yali