Combining Targeted Radionuclide Therapy and Immune Checkpoint Inhibition for Cancer Treatment.
Combining Targeted Radionuclide Therapy and Immune Checkpoint Inhibition for Cancer Treatment.
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DOI：
10.1158/1078-0432.ccr-21-4332
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发表时间：
2022-09-01
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免疫疗法的发展，特别是免疫检查点抑制剂（ICI），在过去几十年中彻底改变了癌症治疗。然而，它的疗效仍然局限于癌症患者的亚组。因此，需要有效的治疗组合策略。在这里，放射治疗是非常有前途的，因为它可以诱导免疫原性细胞死亡，触发促炎细胞因子的释放，从而产生免疫原性表型并使肿瘤对ICI敏感。最近，靶向放射性核素治疗（TRT）已获得显着的兴趣，用于癌症治疗。在这种方法中，肿瘤靶向放射性药物用于向所有肿瘤细胞（包括远处转移性病变）特异性递送治疗辐射剂量，同时限制对健康组织的辐射暴露。然而，TRT和常规放疗之间的根本差异使得不可能直接从常规放疗外推到TRT的生物学效应。在这篇综述中，我们提出了一个全面的概述研究调查的免疫调节作用的TRT和TRT-ICI联合治疗的疗效。临床前研究已经评估了各种鼠癌症模型，其中α或β发射放射性核素被定向到不同的靶点。此外，正在进行临床试验，以评估联合TRT-ICI在癌症患者中的安全性和疗效。总之，研究表明，TRT和ICI联合使用可能会改善癌症患者的治疗反应。未来的研究必须揭示在剂量和治疗方案方面的最佳条件是什么，以最大限度地提高这种联合方法的疗效。
The development of immunotherapy, in particular immune checkpoint inhibitors (ICI), has revolutionized cancer treatment in the past decades. However, its efficacy is still limited to subgroups of patients with cancer. Therefore, effective treatment combination strategies are needed. Here, radiotherapy is highly promising, as it can induce immunogenic cell death, triggering the release of pro-inflammatory cytokines, thereby creating an immunogenic phenotype and sensitizing tumors to ICI. Recently, targeted radionuclide therapy (TRT) has attained significant interest for cancer treatment. In this approach, a tumor-targeting radiopharmaceutical is used to specifically deliver a therapeutic radiation dose to all tumor cells, including distant metastatic lesions, while limiting radiation exposure to healthy tissue. However, fundamental differences between TRT and conventional radiotherapy make it impossible to directly extrapolate the biological effects from conventional radiotherapy to TRT. In this review, we present a comprehensive overview of studies investigating the immunomodulatory effects of TRT and the efficacy of combined TRT-ICI treatment. Preclinical studies have evaluated a variety of murine cancer models in which α- or β-emitting radionuclides were directed to a diverse set of targets. In addition, clinical trials are ongoing to assess safety and efficacy of combined TRT-ICI in patients with cancer. Taken together, research indicates that combining TRT and ICI might improve therapeutic response in patients with cancer. Future research has to disclose what the optimal conditions are in terms of dose and treatment schedule to maximize the efficacy of this combined approach.