Fullerene Immunoconjugates for Cancer Imaging and Treatment

用于癌症成像和治疗的富勒烯免疫偶联物

• 批准号: 7272908
• 负责人: ROBERT D BOLSKAR
• 金额: $ 20.09万
• 依托单位: TDA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-26 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7272908
• 关键词: Antibodies; Antineoplastic Agents; Area; Cancer Center; Cancerous; Carbon; Cells; Chemistry; Class; Collaborations; Condition; Contrast Media; Development; Diagnosis; Doctor of Medicine; Drug Kinetics; Evaluation; Excretory function; Fullerenes; Goals; Government; Image; Immunoconjugates; In Vitro; Investigation; Label; Magnetic Resonance Imaging; Malignant Neoplasms; Melanoma Cell; Metabolic; Metastatic Melanoma; Neoplasm Metastasis; Outcome; Paclitaxel; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Prodrugs; Production; Purpose; Relaxation; Research; Rice; Role; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Staging; Testing; Therapeutic; Therapeutic Agents; Time; Toxic effect; Transfection; Universities; antibody conjugate; caged molecule; cancer cell; cancer imaging; cytotoxic; cytotoxicity; experience; fullerene C60; improved; macromolecule; melanoma; nanoparticle; pre-clinical; success; therapeutic target; uptake

DESCRIPTION (provided by applicant): In this collaborative project between TDA Research, Rice University and M.D. Anderson Cancer Center, we will develop new metallofullerene-taxol-antibody conjugates for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry useful for conjugating drug molecules, to generate therapeutic prodrugs. The endohedral metallofullerene Gd@C60 have been shown in prior studies to function effectively as T1 imaging agents, including for cellular labeling. Gd@C60 offers a safe contrast agent platform lacking the potential for free Gd3+ toxicity due to the very high stability of endohedral Gd sequestration, which is not compromised under physiological conditions. We will chemically conjugate paclitaxel groups to a Gd@C60 derivative to form a new combined therapeutic/imaging agent prodrug. Using the Gd@C60-paclitaxel conjugates, new immunoconjugates with the anti-gp240 melanoma antibody ZME-018 will be formed and tested for cellular uptake, for MRI contrast agent efficacy and for cytotoxicity against melanoma cancer cells in vitro. The strategy of combining antibody targeting with a therapeutic MR imaging agent will improve melanoma diagnosis, treatment and patient outcome, and has the potential for targeting multiple drugs to cancerous cells at the same time.

描述（由申请人提供）：在TDA研究，赖斯大学和医学博士之间的合作项目中，安德森癌症中心，我们将开发新的金属富勒烯-紫杉醇-抗体结合物，用于联合癌症成像和治疗。富勒烯是无毒的碳笼分子，具有丰富的衍生化化学，可用于缀合药物分子以产生治疗前药。内嵌金属富勒烯Gd@C60在先前的研究中已经显示出作为T1成像剂的有效功能，包括用于细胞标记。Gd@C60提供了一种安全的造影剂平台，由于在生理条件下不受损害的非常高的内生Gd螯合稳定性，因此没有游离Gd 3+毒性的可能性。我们将紫杉醇基团与Gd@C60衍生物化学缀合以形成新的组合治疗/成像剂前药。使用Gd@C60-紫杉醇缀合物，将形成具有抗gp 240黑素瘤抗体ZME-018的新免疫缀合物，并测试细胞摄取、MRI造影剂功效和体外针对黑素瘤癌细胞的细胞毒性。将抗体靶向与治疗性MR成像剂相结合的策略将改善黑色素瘤的诊断、治疗和患者结局，并且具有同时将多种药物靶向癌细胞的潜力。