In Situ Tumor Vaccination with Calcium‐Linked Degradable Coacervate Nanocomplex Co‐Delivering Photosensitizer and TLR7/8 Agonist to Trigger Effective Anti‐Tumor Immune Responses
In Situ Tumor Vaccination with Calcium‐Linked Degradable Coacervate Nanocomplex Co‐Delivering Photosensitizer and TLR7/8 Agonist to Trigger Effective Anti‐Tumor Immune Responses
复制标题
使用钙联可降解凝聚纳米复合物共同递送光敏剂和 TLR7/8 激动剂进行原位肿瘤疫苗接种，以触发有效的抗肿瘤免疫反应
DOI：
10.1002/adhm.202102781
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发表时间：
2022
影响因子：
10
通讯作者：
Zhiyue Zhang
中科院分区：
文献类型：
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作者：
Yutong Liu;Hui Li;Huajun Zhao;Y. Hao;Simon Van Herck;Zejun Xu;Guan Wang;Xiao Wang;Xinke Zhang;Xiaoyan Ge;Xia Li;Ailu Yang;Hongfei Chen;Jing Zou;Wentao Wang;B. D. De Geest;Zhiyue Zhang
原位抗肿瘤疫苗是一种很有吸引力的肿瘤免疫治疗方法，它依靠树突状细胞(DC)吞噬肿瘤抗原，活化，并将抗原呈递给淋巴组织中的T细胞。本文报道了一种基于Toll样受体(TLR)7/8激动剂或光敏剂偶联的钙交联聚天冬氨酸的多功能纳米复合体。肿瘤内给予纳米复合体后，激光照射诱导细胞杀伤，从而产生一批肿瘤相关抗原库，同时促进肿瘤引流淋巴结中DC的成熟和T细胞的扩增。在原发部位和远端部位都观察到肿瘤生长受到抑制，从而暗示成功地诱导了适应性抗肿瘤反应。这一策略有望在手术前和手术后应用于治疗，利用患者自身肿瘤的突变组来建立免疫记忆，以清除残留的肿瘤细胞和转移。
In situ anti‐tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll‐like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor‐associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor‐draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti‐tumor response. This strategy holds promise for therapeutic application in a pre‐operative and post‐operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.