Fullerene Immunoconjugates for Cancer Imaging and Treatment

描述(申请人提供)：在这个由TDA Research、莱斯大学和M.D.安德森癌症中心合作的项目中，我们将开发用于癌症成像和治疗相结合的新型金属富勒烯-紫杉醇-抗体结合物。富勒烯是一种无毒的碳笼分子，具有丰富的衍生化学，可用于偶联药物分子，生成治疗性前药。先前的研究表明，面体内金属富勒烯Gd@C60可以有效地作为T1显像剂，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Gd在生理条件下不会被破坏，因此没有Gd3毒性的可能性，这是因为内面体Gd隔离非常稳定。我们将把紫杉醇基团化学偶联到Gd@C60衍生物上，形成一种新的联合治疗/显像剂前药。使用Gd@C60-紫杉醇结合物，将与抗gp240黑色素瘤抗体ZME-018形成新的免疫结合物，并在体外测试细胞摄取、磁共振造影剂效力和对黑色素瘤癌细胞的细胞毒性。将抗体靶向与治疗性磁共振成像剂相结合的策略将改善黑色素瘤的诊断、治疗和患者预后，并有可能同时针对癌细胞使用多种药物。

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.