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首页> 美国卫生研究院文献>Neuro-Oncology >TMIC-39. DEVELOPMENT OF CD11b TRACER FOR THE IMMUNE PET IMAGING IN GLIOBLASTOMA MODEL - COULD BE A GAME CHANGER FOR IMMUNOTHERAPY APPROACHES
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TMIC-39. DEVELOPMENT OF CD11b TRACER FOR THE IMMUNE PET IMAGING IN GLIOBLASTOMA MODEL - COULD BE A GAME CHANGER FOR IMMUNOTHERAPY APPROACHES

机译：TMIC-39。 CD11B示踪剂在胶质母细胞瘤模型中的免疫宠物成像 - 可以是免疫治疗方法的游戏变频器

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Glioblastoma is a lethal brain tumor, heavily infiltrated by tumor-associated myeloid cells (TAMCs). As up to 30% of a glioma cellular mass may be attributed to immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). TAMCs impede natural and immunotherapy-driven anti-tumor responses, they are a high-priority and promising therapeutic target currently being evaluated in clinical trials. Multiple preclinical and clinical trials have attempted to target these cells, however monitoring of biologic responses to therapy remains a challenge. Quantifying real time status of MDSCs and TAMs at the tumor site using non-invasive immunoPET could improve therapeutic response and allow for better patient stratification and monitoring of targeted treatment responses. TAMCs highly expressed the cell surface marker, integrin CD11b (Mac-1, αMβ2) and may be a highly effective imaging target for immunoPET strategies. The human/mouse cross-reactive anti-CD11b antibody (clone M1/70) was radiolabeled with 89Zr for PET imaging. PET/CT imaging, with or without a blocking dose of anti-CD11b Ab, was performed in mice bearing established orthotopic syngeneic GL261 gliomas. Flow cytometry and histology in tissues collected from post-imaging biodistribution validated targeting of CD11b+ MDSCs and TAMs. There was significant Zr-89-anti-CD11b Ab uptake in the tumor ipsilateral right brain (SUVmean = 2.6 ± 0.24) compared to contralateral left brain (SUVmean = 0.6 ± 0.11). Blocking with 10-fold lower specific activity 89Zr-anti-CD11b Ab reduced the SUV in right brain with (SUVmean = 0.11 ± 0.06). Immune rich organs spleen and lymph nodes showed high uptake. These results correlated with biodistribution analysis. CD11b expression in the right and left brain were validated using flow cytometry, H&E and IHC, showing high CD11b expression in the right brain. Imaging TAMs and MDSCs with 89Zr-labeled anti-CD11b Ab targeting was validated in a mouse model of malignant gliomas, demonstrating the feasibility of monitoring immune response during immunotherapy.
机译：胶质母细胞瘤是一种致命的脑肿瘤，受到肿瘤相关的骨髓细胞（TAMC）的严重渗透。高达30％的胶质瘤细胞质量可归因于免疫抑制骨髓细胞，包括粘粒源性抑制细胞（MDSC）和肿瘤相关的巨噬细胞（TAMS）。 TAMCS阻碍了自然和免疫疗法驱动的抗肿瘤反应，它们是目前在临床试验中评估的高优先级和有前途的治疗目标。多种临床前和临床试验试图靶向这些细胞，然而监测对治疗的生物反应仍然是一个挑战。使用非侵入性免疫素在肿瘤部位的MDSC和TAMS的实时状态可以改善治疗反应，并允许更好的患者分层和监测有针对性的治疗反应。 Tamcs高度表达细胞表面标记，整合蛋白CD11b（MAC-1，αmβ2），并且可以是免疫素策略的高效成像目标。将人/小鼠交叉反应性抗CD11B抗体（克隆M1 / 70）与89 ZR放射起来，用于PET成像。在成立的原位同工GL261 Gliomas的小鼠中进行PET / CT成像，有或没有阻断剂量的抗CD11b Ab进行。从成像生物分布后的组织中的流式细胞术和组织学验证了CD11b + MDSC和TAMS的靶向。与对侧左脑（Suvmean = 0.6±0.11）相比，肿瘤同侧右脑（Suvmean = 2.6±0.24）中存在显着的ZR-89-抗CD11B AB（Suvmean = 2.6±0.24）。堵塞10倍的较低特异性活性89ZR-抗CD11b AB，用（SUVMEAN = 0.11±0.06）减少了右脑中的SUV。免疫富含器官脾脏和淋巴结显示出高吸收。这些结果与生物分布分析相关。使用流式细胞术，H＆E和IHC验证右和左脑中的CD11b表达，显示在右脑中的高CD11b表达。在恶性胶质瘤的小鼠模型中验证了具有89 ZR标记的抗CD11b AB靶向的成像TAMS和MDSC，证明了免疫治疗期间监测免疫应答的可行性。

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