肿瘤细胞治疗研究
英文原题：Initial insights into the interaction of antibodies radiolabeled with Lutetium-177 and Actinium-225 with tumor microenvironment in experimental human and canine osteosarcoma.
IHC显示，经225 Ac-和177 Lu标记的IF3抗体治疗后，IGF2R阳性OS细胞和OS干细胞群体减少。值得注意的是，放射性标记的IF3抗体有效减少了促肿瘤M2巨噬细胞，突显了其治疗前景。该研究还揭示了自然杀伤（NK）细胞和M1巨噬细胞的多样反应，阐明了TME中复杂的相互作用。在RIT后24和72小时，用[ 177 Lu]Lu-IF3和[ 225 Ac]Ac-IF3治疗的犬Gracie和人OS-33肿瘤中观察到γ-H2AX染色的时间依赖性增加。主要结论：这些发现表明，放射性标记抗体为个性化OS治疗提供了一条有希望的途径，强调了理解其对TME的影响以及与免疫疗法潜在协同作用的重要性。
骨肉瘤（OS）是一种常见的原发性骨癌，影响人类和犬类。本研究描述了人源单克隆抗体IF3与胰岛素样生长因子2受体（IGF2R）结合后，分别用发射α粒子的锕-225（225 Ac）或发射β粒子的镥-177（177 Lu）放射性核素标记，在实验性人源和犬源OS中与OS细胞及肿瘤微环境（TME）相互作用的初步见解。基本程序：荷有犬源Gracie或人源OS-33 OS肿瘤的SCID小鼠接受177 Lu-或225 Ac标记的IF3抗体治疗，在治疗后24、72或168小时处死，并通过免疫组织化学（IHC）分析其肿瘤中OS细胞的存在、TME的各种元素以及通过γH2AX和caspase 3检测评估DNA双链断裂。
IHC显示，经225 Ac-和177 Lu标记的IF3抗体治疗后，IGF2R阳性OS细胞和OS干细胞群体减少。值得注意的是，放射性标记的IF3抗体有效减少了促肿瘤M2巨噬细胞，突显了其治疗前景。该研究还揭示了自然杀伤（NK）细胞和M1巨噬细胞的多样反应，阐明了TME中复杂的相互作用。在RIT后24和72小时，用[ 177 Lu]Lu-IF3和[ 225 Ac]Ac-IF3治疗的犬Gracie和人OS-33肿瘤中观察到γ-H2AX染色的时间依赖性增加。主要结论：这些发现表明，放射性标记抗体为个性化OS治疗提供了一条有希望的途径，强调了理解其对TME的影响以及与免疫疗法潜在协同作用的重要性。
BACKGROUND: Osteosarcoma (OS) is a prevalent primary bone cancer affecting both humans and canines. This study describes initial insights into the interaction of the human monoclonal antibody IF3 to an insulin-like growth factor 2 receptor (IGF2R) radiolabeled with either alpha-emitting Actinium-225 ( 225 Ac) or beta-emitting Lutetium-177 ( 177 Lu) radionuclides with the OS cells and tumor microenvironment (TME) in experimental human and canine OS. BASIC PROCEDURES: SCID mice bearing canine Gracie or human OS-33 OS tumors were treated with 177 Lu- or 225 Ac-labeled IF3 antibody, sacrificed at 24, 72 or 168 h post-treatment and their tumors were analyzed by immunohistochemistry (IHC) for the presence of OS cells, various elements of TME as well as for the double DNA strand breaks with γH2AX and caspase 3 assays. MAIN FINDINGS: IHC revealed a reduction in IGF2R-positive OS cells and OS stem cell populations post therapy with 225 Ac- and 177 Lu-labeled IF3 antibody. Notably, radiolabeled IF3 antibody effectively diminished pro-tumorigenic M2 macrophages, highlighting its therapeutic promise. The study also unveiled varied responses of natural killer (NK) cells and M1 macrophages, shedding light on the intricate TME interplay. Time-dependent increase in γ-H2AX staining in canine Gracie and human OS-33 tumors treated with [ 177 Lu]Lu-IF3 and [ 225 Ac]Ac-IF3 was observed at 24 and 72 h post-RIT. PRINCIPAL CONCLUSIONS: These findings suggest that radiolabeled antibodies offer a hopeful avenue for personalized OS treatment, emphasizing the importance of understanding their impact on the TME and potential synergies with immunotherapy.
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