Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants.
Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants.
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DOI：
10.3389/fonc.2018.00056
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发表时间：
2018
影响因子：
4.7
通讯作者：
Ngwa W
中科院分区：
文献类型：
--
作者：
Moreau M;Yasmin-Karim S;Kunjachan S;Sinha N;Gremse F;Kumar R;Chow KF;Ngwa W
在这项研究中，我们研究了使用多功能智能放射治疗生物材料（SRB）加载免疫佐剂，以提高局部放射治疗（RT）的远位效应。SRB的设计类似于目前使用的惰性RT生物材料，将可生物降解的聚合物与用于装载免疫佐剂抗CD40单克隆抗体的有效载荷的储库结合。在每只小鼠的右胁腹和左胁腹均产生肺（LLC 1）肿瘤，其中左侧肿瘤代表转移。将小鼠随机分为8个组群，其中4个组群接受5戈伊的图像引导RT（IGRT），另外4个组群接受0戈伊的图像引导RT。IGRT和计算机断层扫描（CT）成像使用小动物辐射研究平台（SARRP）进行。在25周内评估了侧腹肿瘤的肿瘤体积测量值和动物生存率。肿瘤体积测量显示，在用负载有CD40 mAb和IGRT的SRB处理的组群中，小鼠右胁腹肿瘤的生长抑制显著增强。结果还表明，使用聚合物SRB与CD40单克隆抗体而不使用RT可以产生免疫应答，这与使用抗CD40时显示这种应答的先前研究一致。总体而言，60%的用SRB治疗的小鼠在观察期内显示出完全的肿瘤消退，相比之下，用抗CD40 mAb但没有SRB施用的队列为10%。在任何其他队列中均未观察到肿瘤完全消退。这些发现证明了更多的研究不同的RT剂量和量化的免疫细胞群体时，使用SRB。可以开发这种SRB来替代目前使用的RT生物材料，不仅允许RT期间的几何准确性，而且还允许将RT扩展到转移性病变的治疗。
In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions.
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