In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma.
In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma.
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DOI：
10.1158/2159-8290.cd-18-0743
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发表时间：
2018-10
期刊：
影响因子：
28.2
通讯作者：
Levy R
中科院分区：
文献类型：
--
作者：
Frank MJ;Reagan PM;Bartlett NL;Gordon LI;Friedberg JW;Czerwinski DK;Long SR;Hoppe RT;Janssen R;Candia AF;Coffman RL;Levy R
这项多中心1/2期临床试验评估了TLR9激动剂SD-101和低剂量放疗在未经治疗的惰性淋巴瘤患者中的应用。29例入组患者接受4 Gy的放射治疗，随后每周5次在单个肿瘤部位注射SD-101。未发生与治疗相关的4级或严重不良事件。几乎所有患者的治疗部位都有肿瘤缩小。更重要的是，24名患者在未治疗部位肿瘤缩小，5名患者达到部分缓解，1名患者达到完全缓解。在肿瘤微环境中观察到与治疗相关的CD8+和CD4+效应T细胞的增加和T滤泡辅助细胞和T调节细胞（Tregs）的减少。治疗前低水平的CD4+ Tregs、增殖的CD8+ t细胞和GranzymeB+ CD8+ t细胞与良好的结果相关。肿瘤内SD-101联合低剂量辐射耐受性良好，治疗和未治疗的疾病部位均可消退。
This multicenter phase 1/2 clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. 29 enrolled patients received 4 Gy of radiation followed by five weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their non-treated sites with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T-cells and decreases of T Follicular Helper and T regulatory cells (Tregs) were observed in the tumor microenvironment. Low pre-treatment levels of CD4+ Tregs, proliferating CD8+ T-cells, and GranzymeB+ CD8+ T-cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease.