Growth Factor Imaging and Photoimmunotherapy

该项目涵盖了分子成像计划的许多部分。我们一直并将继续专注于开发膜受体靶向药物，以诊断，分期和选择患者进行治疗。除了上述试剂之外，另一类成像剂基于抗体。我们已经开发了多种放射性标记抗体，并完成了几项涉及它们的临床试验。此外，我们还开发了一种称为光免疫疗法（PIT）的新疗法，该疗法将特定的光子吸收染料IR 700与抗体结合。然后注射该抗体光子吸收剂缀合物（APC）并结合肿瘤细胞表面上的同源受体。暴露于近红外光（NIR）产生快速和选择性的癌细胞杀伤。PIT是我们团队在2010年发现的，并进行了多个动物模型。到2013年，这项发明被授权给Aspyrian，现在是乐天。在过去的几年中，已经进行了头颈癌的I期和II期研究，复发性头颈癌的客观缓解率为44%。已经看到了几个长期的幸存者。PIT目前正在全球进行第三阶段测试，并于2020年底在日本获得批准。与此同时，我们正在开发靶向免疫抑制细胞的PIT，希望能促进比肿瘤PIT引起的更强的免疫反应。例如，当Treg PIT与抗肿瘤PIT在小鼠模型中组合时，观察到强免疫原性应答，诱导记忆T细胞，防止肿瘤的进一步植入。我们正在微观水平上研究小鼠模型中的这种现象，以更好地了解从肿瘤微环境中去除T reg细胞如何特异性地导致T细胞介导的细胞杀伤。与此同时，我们继续作为一个计划，开发有针对性的小分子和抗体缀合物的PET成像。我们正在CC NIH启动一项临床试验，将PIT用作可手术头颈癌患者手术前的新辅助治疗。已经开发了一种用于杀死Treg细胞的CD25抗体，目前正在制造用于人体试验。当与肿瘤靶向PIT组合时，该药剂将引起对PIT的免疫应答的显著增加，从而导致更深刻的治疗效果。

This project spans many parts of the molecular imaging program. We have been and continue to be focused on developing membrane receptor targeted agents in order to diagnose, stage and select patients for therapy. In addition to the agents described above, one other class of imaging agents is based on antibodies. We have developed multiple radiolabeled antibodies and have completed several clinical trials involving them. In addition we have developed a novel therapy called photoimmunotherapy (PIT) that conjugates a specific photon absorbing dye, IR700 to an antibody. This antibody photon absorber conjugate (APC) is then injected and binds to the cognate receptor on the tumor cell surface. Exposure to near infrared light (NIR) produces a rapid and selective cancer cell killing. PIT was discovered by our team in 2010 and multiple animal models were undertaken. By 2013 the invention was licensed to Aspyrian which is now Rakuten. Over the past several years Phase 1 and Phase II studies in head and neck cancers have been performed with a 44% objective response rate in recurrent head and neck cancers. Several long term survivors have been seen. PIT is now in global Phase 3 testing and was approved in Japan in late 2020. Meanwhile we are developing PIT that targets immunosuppressive cells in the hopes of promoting an even stronger immune response than is evoked by PIT of the tumor. When, for instance, Treg PIT is combined with anti tumor PIT in mouse models strong immunogenic responses are seen with induction of memory T cells preventing further implantation of the tumor. We are studying this phenomenon in mouse models at the microscopic level to better understand how removing T reg cells from the tumor microenvironment specifically causes T cell mediated cell killing. At the same time we continue as a program to develop targeted small molecule and antibody conjugates for PET imaging. We are initiating a clinical trial in the CC NIH to use PIT as a neoadjuvant therapy prior to surgery in patients with operable head and neck cancers. A CD25 antibody for killing Treg cells has been developed and is currently being manufactured for use in human trials. This agent, when combined with a tumor targeted PIT will cause a substantial increase in the immune response to PIT leading to more profound treatment effects.