RECOMBINANT ANTIBODIES AGAINST PROSTATE CANCER ANTIGENS

抗前列腺癌抗原的重组抗体

• 批准号: 7561507
• 负责人: MYRON NV WILLIAMS
• 金额: $ 7.8万
• 依托单位: CLARK ATLANTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7561507
• 关键词: Affinity; Antibodies; Antigens; Archives; Benign Prostatic Hypertrophy; Binding; Biological; Biological Assay; Biological Markers; Biopsy Specimen; Cancer Patient; Cell Line; Cell Separation; Cell surface; Cells; Computer Retrieval of Information on Scientific Projects Database; Condition; Cultured Cells; Development; Diagnosis; Diagnostic; Early Diagnosis; Funding; Gene Proteins; Grant; Growth; Hybridomas; Institution; Intervention; Ki-ras Gene; Knowledge; Libraries; Localized; Malignant neoplasm of prostate; Methods; Monoclonal Antibodies; Nature; Numbers; Outcome Study; Phage Display; Post-Translational Protein Processing; Prostate; Prostate Adenocarcinoma; Prostate-Specific Antigen; Prostatic; Prostatic Diseases; Radical Prostatectomy; Recombinant Antibody; Research; Research Personnel; Resources; Serum; Source; Specificity; Techniques; Testing; Therapeutic; Tumorigenicity; United States National Institutes of Health; Urine; Work; cell type; macromolecule; mortality; novel; novel therapeutics; protein expression; therapeutic target; tumorigenic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although an immunochemical test for prostate specific antigen (PSA) test has proved valuable for early diagnosis of prostate adenocarcinoma (PCa), elevated PSA levels are also seen in a number of other prostatic conditions that have distinct therapeutic requirements, such as benign prostate hyperplasia (BPH). Biomarkers other than PSA that can be assessed in biopsy specimens, in serum or in urine will be valuable in determining the appropriate strategy for intervention. Monoclonal antibodies (MAbs) provide a rapid and specific means of detecting the presence of biomarkers, independent of whether they result from changes in gene and protein expression, or from biological modification of proteins or other macromolecules. We propose to isolate antibodies that recognize novel biomarkers associated with tumorigenic potential of prostate cells. The underlying hypothesis of this work is that detectable antigens are differentially expressed in prostate cells as they become oncogenically transformed. Identification of these antigens, some of which are likely to be present on the surfaces of cells, may be performed using paired cell lines that differ in tumorigenic potential. Although MAbs can be easily used to distinguish antigens on cells, isolation of MAbs by traditional, hybridoma methods is difficult in the absence of purified antigen. Antibody phage display permits the use of affinity subtraction and purification techniques for selection of MAbs (Aim 1) binding to antigens that differ between closely related cell types, even without prior knowledge of the nature of the antigens involved. Lineage-related human prostate cell lines, RWPE-1 and RWPE-2, which differ in the absence/presence of a Ki-Ras gene, are an ideal platform for identification of tumorigenicity-associated antigens. Antibody phage display libraries will be subtracted on RWPE-1 and selected on RWPE-2 cell lines. MAbs identified in this manner will be verified for their specificity (Aim 3) for tumorigenic cultured cells, and their cognate antigens characterized (Aim 2). Archived serum, radical prostatectomy and biopsy specimens from localized and metastatic PCa will be probed with the novel MAbs to determine the scope of expression of the antigens in cancer patients. The primary outcome of this study will be novel antibodies against biomarkers associated with tumorigenic prostate disease. This will have an impact on diagnosis and treatment of prostatic cancer in that they will permit the development of diagnostic assays that can predict the tumorous potential of abnormal prostatic growth. Antibodies or other molecules directed against these antigens may also prove novel therapeutic targets and thus have the potential to dramatically reduce mortality.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尽管对前列腺特异性抗原（PSA）测试的免疫化学测试已被证明对于早期诊断前列腺腺癌（PCA）很有价值，但在许多具有独特的治疗要求的其他前列腺疾病中也可以看到升高的PSA水平，例如良性前列腺增生（BPH）。 可以在活检标本，血清或尿液中评估的PSA以外的生物标志物对于确定适当的干预策略是有价值的。 单克隆抗体（mAb）提供了一种快速而特定的检测生物标志物的方法，与它们是由于基因和蛋白质表达的变化而导致的，还是蛋白质或其他大分子的生物学修饰。 我们建议分离识别与前列腺细胞肿瘤性潜力相关的新生物标志物的抗体。 这项工作的基本假设是，随着肿瘤的发生，可检测到的抗原在前列腺细胞中差异表达。 这些抗原的鉴定，其中一些可能存在于细胞表面上，可以使用肿瘤势不同的成对细胞系进行。 尽管可以轻松地使用mAb来区分细胞上的抗原，但在没有纯化的抗原的情况下，很难通过传统的传统杂交瘤方法分离mAb。 抗体噬菌体显示允许使用亲和力减法和纯化技术来选择mAb（目标1）与紧密相关的细胞类型之间有所不同的抗原结合，即使没有事先了解所涉及的抗原的性质。 与谱系相关的人前列腺细胞系RWPE-1和RWPE-2在不存在/存在Ki-Ras基因的情况下是鉴定肿瘤性相关抗原的理想平台。 抗体噬菌体显示库将在RWPE-1上减去，并在RWPE-2细胞系上选择。 以这种方式鉴定的单元对肿瘤培养细胞的特异性（AIM 3）将得到验证，其同源抗原的表征（AIM 2）。 将用新型mAB探测来自局部和转移性PCA的归档血清，根治性前列腺切除术和活检标本，以确定癌症患者中抗原表达的范围。 这项研究的主要结果是针对与肿瘤性前列腺疾病相关的生物标志物的新型抗体。 这将对前列腺癌的诊断和治疗产生影响，因为它们将允许开发诊断测定，以预测异常前列腺生长的肿瘤潜力。 针对这些抗原的抗体或其他分子也可能证明新的治疗靶标，因此有可能大大降低死亡率。