Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination.
Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination.
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DOI：
10.1039/d2bm00403h
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发表时间：
2022-08-09
影响因子：
6.6
通讯作者：
Jewell, Christopher M.
中科院分区：
文献类型：
--
作者：
Andorko, James, I;Tsai, Shannon J.;Gammon, Joshua M.;Carey, Sean T.;Zeng, Xiangbin;Gosselin, Emily A.;Edwards, Camilla;Shah, Shrey A.;Hess, Krystina L.;Jewell, Christopher M.
最近批准的癌症免疫疗法-包括CAR-T细胞和癌症疫苗-显示出巨大的希望。然而，这些技术受到离体分离和工程化患者细胞的复杂性和成本的阻碍。淋巴结（LN）是整合免疫信号以协调适应性免疫的关键组织。直接控制LN中的信号和局部环境可以实现有效和安全的免疫治疗，而无需细胞分离，工程和再输注。在这里，我们采用LN（i. LN.）注射免疫信号加载的生物材料库以直接控制癌症疫苗沉积，揭示了LN中和LN之间的信号的组合和地理分布如何影响抗肿瘤反应。我们在健康和患病小鼠中发现，LN中抗原和佐剂的相对接近-以及肿瘤-定义了先天性和适应性反应的独特局部和全身特征。这些因素最终控制淋巴瘤和黑素瘤小鼠模型的存活率。值得注意的是，利用适当的地理信号分布，单个i. LN.疫苗治疗使肿瘤攻击和100天后再攻击几乎完全存活，而无需额外的治疗。这些数据为免疫疗法的设计标准提供了信息，这些免疫疗法利用生物材料进行局部LN治疗，以产生全身性和特异性的反应，而不会使患者全身暴露于强效或免疫毒性药物。淋巴结（LN）中的局部信号整合控制着细胞移入和移出LN时全身反应的效力和选择性。在这里，LN内储库用于在治疗的LN和未治疗的LN内空间定向通信，并且全身性地，引起可编程的和发散的免疫治疗结果。局部控制这些过程可以实现有效的癌症免疫治疗，而无需全身暴露于免疫毒性药物。
Recently approved cancer immunotherapies – including CAR-T cells and cancer vaccination, – show great promise. However, these technologies are hindered by the complexity and cost of isolating and engineering patient cells ex vivo. Lymph nodes (LNs) are key tissues that integrate immune signals to coordinate adaptive immunity. Directly controlling the signals and local environment in LNs could enable potent and safe immunotherapies without cell isolation, engineering, and reinfusion. Here we employ intra-LN (i.LN.) injection of immune signal-loaded biomaterial depots to directly control cancer vaccine deposition, revealing how the combination and geographic distribution of signals in and between LNs impact anti-tumor response. We show in healthy and diseased mice that relative proximity of antigen and adjuvant in LNs - and to tumors - defines unique local and systemic characteristics of innate and adaptive response. These factors ultimately control survival in mouse models of lymphoma and melanoma. Of note, with appropriate geographic signal distributions, a single i.LN. vaccine treatment confers near-complete survival to tumor challenge and re-challenge 100 days later, without additional treatments. These data inform design criteria for immunotherapies that leverage biomaterials for loco-regional LN therapy to generate responses that are systemic and specific, without systemically exposing patients to potent or immunotoxic drugs. Local signal integration in lymph nodes (LNs) controls the potency and selectivity of systemic responses as cells migrate in and out of LNs. Here, intra-LN depots were used to spatially direct communication within treated LNs and untreated LNs, and systemically, causing programmable and divergent immunotherapy outcomes. Locally controlling these processes could enable effective cancer immunotherapies without systemic exposure to immunotoxic drugs.
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DOI：
10.1038/s41577-019-0269-6
发表时间：
2020-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Irvine DJ;Dane EL
通讯作者：
Dane EL
影响因子：
10.9
作者：
Angela Aznar, M.;Planelles, Lourdes;Melero, Ignacio
通讯作者：
Melero, Ignacio
影响因子：
15.9
作者：
Antonelli, Lis R. V.;Rothfuchs, Antonio Gigliotti;Sher, Alan
通讯作者：
Sher, Alan
影响因子：
12.4
作者：
Adamina, Michel;Rosenthal, Rachel;Zajac, Paul
通讯作者：
Zajac, Paul
DOI：
10.1073/pnas.1105200108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Jewell, Christopher M.;Lopez, Sandra C. Bustamante;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.