Novel Platform Technology for Developing Therapeutic Human mAbs

用于开发治疗性人类单克隆抗体的新型平台技术

• 批准号: 7277341
• 负责人: Rachel Hannah Kravitz
• 金额: $ 14万
• 依托单位: NEOCLONE BIOTECHNOLOGY INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-21 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277341
• 关键词: Accounting; Advanced Malignant Neoplasm; Adverse effects; Affinity; Agar; Allergic Reaction; Amino Acid Sequence; Antibodies; Antibody-Producing Cells; Antigen Targeting; Antigens; Ascites; Autoimmune Process; B-Lymphocytes; Biotechnology; Carbohydrate Sequence; Cell Cycle; Cell Extracts; Cell Line; Cell Lineage; Cell Separation; Cell Survival; Cells; Characteristics; Chromosomes; Cities; Class; Clinical; Clinical Trials; Communicable Diseases; Core Protein; Cytometry; DNA; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerase; Dendritic Cells; Development; Diagnostics Research; Disease; Drug Delivery Systems; Early Diagnosis; Early treatment; Engineering; Engraftment; Enzyme-Linked Immunosorbent Assay; Evaluation; Figs - dietary; General Population; Genomic Instability; Genomics; Gleevec; Goals; Government; Growth; Her2/erbb2/neu Staining Method; Human; Human Development; Hybridomas; Immune; Immune response; Immunization; Immunoglobulin Genes; Immunoglobulins; In Vitro; International; Laboratories; Lead; Light; Liquid substance; Localized; MYC Family Protein; Malignant Neoplasms; Marketing; Measures; Medicine; Metabolic Clearance Rate; Methods; Mitogens; Modeling; Molecular; Monoclonal Antibodies; Mouse Strains; Multiple Myeloma; Mus; Non-Human Protein; Nucleic Acids; Numbers; Pain; Patients; Pattern; Peptide Sequence Determination; Peripheral Blood Lymphocyte; Persons; Phage Display; Pharmaceutical Preparations; Phase; Phenotype; Plasmacytoma; Ploidies; Polymerase Chain Reaction; Pongidae; Positioning Attribute; Post-Translational Protein Processing; Production; Protein Glycosylation; Proteins; Proteomics; Purpose; Range; Rate; Regulation; Retroviridae; Roche brand of trastuzumab; Rodent; Screening for cancer; Severities; Societies; Sorting - Cell Movement; Specificity; Splenocyte; System; Techniques; Technology; Testing; Text; Therapeutic; Therapeutic Agents; Therapeutic Monoclonal Antibodies; Therapeutic Uses; Therapeutic antibodies; Time; Toxic effect; Transgenes; Transgenic Mice; Transgenic Organisms; United States Food and Drug Administration; Western Blotting; Yeasts; abl Oncogene; anticancer research; base; cancer therapy; cancer type; chemotherapy; cost; cost effective; cytokine; design; drug development; human monoclonal antibodies; immunogenic; immunogenicity; improved; inhibitor/antagonist; leukemia virus; malignant breast neoplasm; mortality; mouse model; novel; novel therapeutics; penis foreskin; protein expression; research and development; research study; response; sarcoma; stable cell line; technology development; tumor

DESCRIPTION (provided by applicant): Despite significant advances in treatment and early detection, cancer remains a significant disease threat to society. Therapeutic monoclonal antibodies are effective new treatments that have recently been developed as targeted therapies against many types of cancer. Over 17 monoclonal antibodies have been approved in the US for treating a variety of diseases. The advantages are high specificity, predictable side effects, and more rapid and less expensive advancement through clinical trials. Significant hurdles remain, however, including the low efficiency of antibody development, instability of hybridoma cell lines, adverse patient immune responses to foreign protein or carbohydrate sequences, and commercially, royalty stacking issues from the need to access the multiple technologies required to develop an efficacious antibody therapeutic. There is currently no technology platform that allows one to develop human monoclonal antibody producing cell lines by direct transformation of human immune cells. Such antibodies can be tested for specific therapeutic characteristics and the cell lines directly scaled for larger antibody manufacturing without the use of additional platform technologies. The approach described herein is one that allows for more rapid discovery of high value therapeutic products, that will both personalize and revolutionize the therapeutic human monoclonal antibody as the new era of genomics and proteomics continues to provide enormous opportunity for the discovery of druggable targets. The objective of this Phase I proposal is utilize the ABL-MYC retroviral transformation technology for the development of fully human monoclonal antibodies. NeoClone has utilized this approach commercially since 1999 to develop murine antibodies for research and diagnostic use. If successful in this proposal, the advantages of our murine antibody technology would hold true: rapid, efficient, cost effective development of high affinity monoclonal antibodies. Additional advantages for therapeutics would be fully human antibody sequence, stable cell lines, accurate post-translational modifications and no need for further maturation to improve affinity. Additionally, this technology would have the potential to use the patient's own cells for antibody development. A more rapid and efficacious therapeutic antibody technology would be a welcome addition to the arsenal of approaches to combat cancer and other deadly diseases. Therapeutic monoclonal antibodies are emerging as one of the most effective targeted drug approaches for cancer. NeoClone is proposing to adapt it's successful monoclonal antibody technology to enable rapid development of fully human therapeutic monoclonal antibodies. The potential advantages of this approach are more rapid and efficient drug development with less potential for deleterious side effects.

描述（由申请人提供）：尽管在治疗和早期检测方面取得了重大进展，癌症仍然是对社会的重大疾病威胁。治疗性单克隆抗体是最近开发的有效的新疗法，可作为针对多种癌症的靶向疗法。美国已批准超过 17 种单克隆抗体用于治疗多种疾病。其优点是特异性高、副作用可预测，以及通过临床试验取得更快、更便宜的进展。然而，仍然存在重大障碍，包括抗体开发效率低、杂交瘤细胞系不稳定、患者对外来蛋白质或碳水化合物序列的不良免疫反应，以及商业上的特许权使用费堆积问题，因为需要获得开发有效抗体所需的多种技术。抗体治疗。目前还没有技术平台允许通过直接转化人类免疫细胞来开发产生人单克隆抗体的细胞系。可以测试此类抗体的特定治疗特性，并且可以直接扩展细胞系以进行更大的抗体生产，而无需使用额外的平台技术。本文描述的方法是一种允许更快速地发现高价值治疗产品的方法，随着基因组学和蛋白质组学的新时代继续为发现可成药靶点提供巨大机会，该方法将个性化和彻底改变治疗性人单克隆抗体。该第一期提案的目标是利用 ABL-MYC 逆转录病毒转化技术开发全人单克隆抗体。 NeoClone 自 1999 年以来一直在商业上利用这种方法来开发用于研究和诊断用途的鼠抗体。如果该提案获得成功，我们的鼠抗体技术的优势将得以体现：快速、高效、经济高效地开发高亲和力单克隆抗体。治疗的其他优势包括完整的人类抗体序列、稳定的细胞系、准确的翻译后修饰以及无需进一步成熟以提高亲和力。此外，这项技术还有可能利用患者自身的细胞来开发抗体。更快速、更有效的治疗性抗体技术将成为对抗癌症和其他致命疾病的方法库中受欢迎的补充。治疗性单克隆抗体正在成为治疗癌症最有效的靶向药物方法之一。 NeoClone 提议采用其成功的单克隆抗体技术，以实现全人源治疗性单克隆抗体的快速开发。这种方法的潜在优点是药物开发更加快速和有效，并且产生有害副作用的可能性较小。