Tissue engineered cancer metastases as cancer vaccine to improve cancer immunotherapy.
Tissue engineered cancer metastases as cancer vaccine to improve cancer immunotherapy.
复制标题
组织工程癌症转移作为癌症疫苗来改善癌症免疫治疗。
DOI：
10.1016/j.actbio.2022.09.059
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发表时间：
2022
影响因子：
9.7
通讯作者：
Wang,AndrewZ
中科院分区：
文献类型：
--
作者：
Sultanpuram,NikhilaReddy;Ahmed,Umer;Peters,JonathanThomas;Zhang,Tian;Wang,AndrewZ
放射治疗经常被用来改善癌症免疫治疗的结果。虽然有临床前和临床数据支持这一方法，但也存在重大挑战。一个关键的挑战是，由于潜在的正常组织毒性和先前的治疗，并不是所有的患者都有可以通过放射治疗轻松治愈的肿瘤。此外，放射外科术后难以控制肿瘤微环境来促进免疫反应。为了克服这些挑战，我们假设我们可以设计癌症转移，并利用辐射工程肿瘤细胞作为个性化癌症疫苗来改进癌症免疫治疗。在这里，我们报告了利用去细胞大鼠肺组织进行工程化肺转移的发展。使用B16F10黑色素瘤肿瘤模型，我们发现放射治疗的工程化转移瘤在改善癌症免疫治疗反应方面非常有效，而且比活体转移更有效。我们的工作证明了组织工程学在肿瘤免疫治疗中的应用潜力。有意义的陈述放射和免疫治疗的联合是治疗转移的有效方法。尽管他们取得了成功，但长期反应仍然很低。肿瘤微环境逃避免疫反应、正常组织对辐射的毒性以及无法进行放射外科治疗是一些限制因素。为了克服这些挑战，在本文中，我们提供了支持使用高剂量辐射治疗的数据-使用脱细胞肺支架构建活体工程B16F10转移模型。这些经过改造的转移瘤与活体肿瘤非常相似，当与Check Point抑制剂一起注射到荷瘤小鼠体内时，在改善癌症免疫治疗反应方面非常有效。
Radiotherapy is often used to improve cancer immunotherapy outcomes. While there are both pre-clinical and clinical data supporting this approach, there are also significant challenges. One key challenge is that not all patients have tumors that can be easily treated with radiotherapy due to potential normal tissue toxicity and prior treatment. In addition, it is difficult to control the tumor microenvironment to promote the immune response after radiosurgery. To overcome these challenges, we hypothesize that we can engineer cancer metastasis and utilize irradiated engineered tumor cells as a personalized cancer vaccine to improve cancer immunotherapy. Herein, we report the development of engineered lung metastasis using decellularized rat lung tissue. Using the B16F10 melanoma tumor model, we showed that radiotherapy-treated engineered metastases are highly effective in improving cancer immunotherapy responses and more effective thanin vivometastasis. Our work has demonstrated the potential of applying tissue engineering to cancer immunotherapy.Statement of significanceCombination of radiation and immunotherapy are an effective way to treat metastasis. Despite their success, long term response still remains low. Tumor microenvironment evading the immune response, normal tissue toxicity to radiation and inaccessibility to radiosurgery are some of the limitations. To overcome these challenges, in this paper we present with data supporting the use of high dose radiation treatedex vivoengineered B16F10 metastasis model using decellularized lung scaffolds. These engineered metastases closely mimic thein vivotumors and when given into tumor bearing mice along with check point inhibitors are highly effective in improving the cancer immunotherapy response.