Fullerene Immunoconjugates for Cancer Imaging and Treatment

用于癌症成像和治疗的富勒烯免疫缀合物

• 批准号: 7501234
• 负责人: ROBERT D BOLSKAR
• 金额: $ 20.7万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7501234
• 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M.D. Anderson癌症中心之间的合作项目中，我们将开发新的金属甲氧苯二酚 - 抗体 - 抗体结合物，用于结合癌症成像和治疗。富勒烯是无毒的碳笼分子，具有丰富的衍生化学化学，可用于结合药物分子，可产生治疗前药。在先前的研究中已经显示了内hallyfullerene GD@C60，可以有效起作用T1成像剂，包括用于细胞标记。 GD@C60提供了一个安全的对比度平台，由于内膜隔离隔离的稳定性很高，因此缺乏可能的游离GD3+毒性，这在生理条件下不会损害。我们将对GD@C60衍生物化学结合紫杉醇基团，形成一种新的组合治疗/成像剂前药。使用GD@C60-丙二酰偶联物，将形成与抗GP240黑色素瘤抗体ZME-018的新免疫偶联物，并测试用于细胞摄取，以获得MRI对比剂效果，并针对抗黑色素瘤细胞的细胞毒性在Viltro中进行MRI对比剂效果。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，并有可能同时将多种药物靶向多种药物。

项目成果

Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast.

• DOI: 10.1038/nnano.2010.203
• 发表时间: 2010-11
• 期刊: Nature nanotechnology
• 影响因子: 38.3

Cell Internalization Studies of Gadofullerene-(ZME-018) Immunoconjugates into A375m Melanoma Cells.

Gadofullerene-(ZME-018) 免疫缀合物进入 A375m 黑色素瘤细胞的细胞内化研究。

• DOI: 10.1593/tlo.11157
• 发表时间: 2011
• 期刊: Translational oncology
• 影响因子: 5
• 作者: Berger,ChristopherScott;Marks,JohnW;Bolskar,RobertD;Rosenblum,MichaelG;Wilson,LonJ
• 通讯作者: Wilson,LonJ