IL-2 scintigraphy as a guide to cancer immunotherapy

IL-2 闪烁扫描术作为癌症免疫治疗的指南

• 批准号: 8547041
• 负责人: SVETOMIR Nenad MARKOVIC
• 金额: $ 30.59万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8547041
• 关键词: Accounting; Address; Antibodies; Autoimmune Diseases; Biopsy; CTLA4 gene; Caliber; Caring; Cells; Clinical; Clinical Trials; Consensus; Cutaneous Melanoma; Data; Detection; Development; Disease Progression; Dose; Down-Regulation; Enrollment; Evaluation; Funding; Future; Health; Histologic; Histology; Human; Image; Immune; Immune response; Immunotherapeutic agent; Infiltration; Inflammation; Interleukin-2; Intestines; Judgment; Label; Lead; Left; Malignant Neoplasms; Measures; Metastatic Melanoma; Methodology; Modification; Needles; Non-Invasive Cancer Detection; Oncologist; Organ; Outcome; Patients; Physicians; Pilot Projects; Procedures; Progression-Free Survivals; Radiolabeled; Radionuclide Imaging; Radiopharmaceuticals; Recommendation; Safety; Solid Neoplasm; Survival Rate; T-Lymphocyte; Testing; Time; Toxic effect; Tumor Volume; Tumor-Infiltrating Lymphocytes; Wit; Work; X-Ray Computed Tomography; autoimmune thyroid disease; base; cancer cell; cancer immunotherapy; clinical practice; experience; human tissue; melanoma; neoplastic cell; peripheral blood; premature; prevent; radiotracer; response; single photon emission computed tomography; tool; tumor; tumor growth; tumor progression; uptake

DESCRIPTION (provided by applicant): The recent FDA approval of ipilimumab (Yervoy(R), anti-CTLA4 antibody) for the treatment of metastatic melanoma and its introduction to clinical practice, have brought to the forefront a long recognized dilemma of cancer immunotherapy: is clinically detectable tumor enlargement the result of tumor infiltration by immune cells (tumor inflammation; good outcome) or an increased number of cancer cells (tumor progression; bad outcome). This is particularly relevant today as ipilimumab (IPI) is in daily clinical practice wit 50% of treated patients with metastatic melanoma facing tumor enlargement within 12 weeks of initiation of treatment. Albeit consensus recommendations do exist to allow for continuation of IPI therapy in the face of limited tumor progression (immune response RECIST criteria), oncologists in clinical practice are left with their best clinical judgment in differentiating tumo inflammation vs. tumor progression. Presently, there are no clinical tools to make this distinction and guide therapy decisions in this unique clinical setting of cancer immunotherapeutics. Over the past decade, work by Dr. Signore et al has resulted in the development of methodology for non-invasive detection of T lymphocyte organ infiltration using interleukin-2 (IL2) based scintigraphy. The group's most recent radiopharmaceutical (99mTc-HYNIC-IL2) builds upon prior IL2 labeling efforts (123I-IL2 and 99mTc-N2S-IL2) using a simplified labeling procedure with excellent detection of activated T lymphocytes in human tissues, including melanoma of the skin. We hypothesize that99mTc-HYNIC-IL2 scintigraphy will allow clinical differentiation of tumor inflammation vs tumor progression in patients undergoing IPI therapy for metastatic melanoma. We seek funding in support of a pilot clinical trial addressing: (1) feasibility/safety of 99mTc-HYNIC-IL2 scintigraphy in patients with metastatic melanoma undergoing IPI therapy; (2) correlation of tumor infiltrating lymphocyte (TIL) invasion assessed by 99mTc-HYNIC-IL2 scintigraphy vs. histology (total and subsets of TIL), as well as screen for peripheral blood correlates; and (3) correlation of TIL invasion (scintigraphy/histology) with tumor diameter (RECIST) and association with 2 year survival. Successful completion of this study will generate necessary preliminary data regarding the utility of 99mTc-HYNIC-IL2 scintigraphy as a guide for IPI therapy in advanced melanoma. We anticipate that 99mTc- HYNIC-IL2 scintigraphy will be able to non-invasively discriminate between tumor progression (low 99mTc- HYNIC-IL2 uptake) vs. tumor inflammation (high99mTc-HYNIC-IL2 uptake) on CT images of tumor masses. The current study will provide necessary data for a future, adequately powered study aimed at establishing the ability of 99mTc-HYNIC-IL2 scintigraphy to predict good clinical outcomes (survival at 2 years) in patients with metastatic melanoma undergoing standard-of-care IPI therapy

描述(由申请人提供)：FDA最近批准ipilimumab(Yerway(R)，抗CTLA4抗体)用于治疗转移性黑色素瘤，并将其引入临床实践，这将癌症免疫治疗中长期以来公认的一个两难境地提了出来：临床上可检测到的肿瘤扩大是由于免疫细胞(肿瘤炎症；良好结果)或肿瘤细胞数量增加(肿瘤进展；不良结果)导致的。这在今天尤其重要，因为ipilimumab(IPI)在日常临床实践中有50%的转移性黑色素瘤患者在开始治疗后12周内肿瘤增大。尽管确实存在共识建议，允许在肿瘤进展有限的情况下继续进行IPI治疗(免疫反应RECIST标准)，但临床实践中的肿瘤学家在区分肿瘤炎症和肿瘤进展方面仍有最佳的临床判断。目前，还没有临床工具来区分这一点。 并在癌症免疫疗法这一独特的临床环境中指导治疗决策。在过去的十年中，SIGNORE博士等人的工作导致了使用基于白细胞介素2(IL2)的核素扫描非侵入性检测T淋巴细胞器官浸润的方法学的发展。该组织最新的放射性药物(99mTC-HYNIC-IL2)建立在之前的IL2标记工作(123I-IL2和99mTC-N2S-IL2)的基础上，使用简化的标记程序，出色地检测到人体组织中激活的T淋巴细胞，包括皮肤黑色素瘤。我们假设99mTC-HYNIC-IL2核素显像可以在临床上区分接受IPI治疗的转移性黑色素瘤患者的肿瘤炎症和肿瘤进展。我们寻求资金支持一项试点临床试验，以解决以下问题：(1)接受IPI治疗的转移性黑色素瘤患者进行99mTC-HYNIC-IL2核素扫描的可行性/安全性；(2)99mTC-HYNIC-IL2核素扫描评估的肿瘤浸润性淋巴细胞(TIL)侵袭性与组织学(TIL总类型和亚类)的相关性，以及筛选外周血相关性；(3)TIL侵袭性(闪烁/组织学)与肿瘤直径(RECIST)的相关性以及与2年生存率的相关性。这项研究的成功完成将产生关于99mTC-HYNIC-IL2核素显像作为晚期黑色素瘤IPI治疗指南的必要的初步数据。我们预计，99mTC-HYNIC-IL2核素显像将能够在肿瘤肿块的CT图像上无创性地区分肿瘤进展(低99mTC-HYNIC-IL2摄取)和肿瘤炎症(高99mTC-HYNIC-IL2摄取)。目前的研究将为未来一项充足的研究提供必要的数据，该研究旨在建立99mTC-HYNIC-IL2核素显像在接受标准护理IPI治疗的转移性黑色素瘤患者中预测良好临床结果(2年存活率)的能力。

项目成果

Non-invasive visualization of tumor infiltrating lymphocytes in patients with metastatic melanoma undergoing immune checkpoint inhibitor therapy: a pilot study.

• DOI: 10.18632/oncotarget.25666
• 发表时间: 2018-07-13
• 期刊: Oncotarget
• 作者: Markovic SN;Galli F;Suman VJ;Nevala WK;Paulsen AM;Hung JC;Gansen DN;Erickson LA;Marchetti P;Wiseman GA;Signore A
• 通讯作者: Signore A