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 Research、莱斯大学和 M.D. 安德森癌症中心之间的合作项目中，我们将开发新的金属富勒烯-紫杉醇-抗体缀合物，用于组合癌症成像和治疗。富勒烯是无毒的碳笼分子，具有丰富的衍生化学性质，可用于缀合药物分子，产生治疗性前药。先前的研究表明，内嵌金属富勒烯 Gd@C60 可以有效地用作 T1 成像剂，包括用于细胞标记。 Gd@C60 提供了一个安全的造影剂平台，由于内嵌 Gd 封存的稳定性非常高，在生理条件下不会受到损害，因此不存在游离 Gd3+ 毒性的可能性。我们将通过化学方式将紫杉醇基团与 Gd@C60 衍生物结合，形成新的组合治疗/显像剂前药。使用 Gd@C60-紫杉醇缀合物，将形成具有抗 gp240 黑色素瘤抗体 ZME-018 的新型免疫缀合物，并在体外测试细胞摄取、MRI 造影剂功效和针对黑色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、治疗和患者结果，并具有同时针对癌细胞靶向多种药物的潜力。

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