In Situ Tumor Vaccination with Calcium‐Linked Degradable Coacervate Nanocomplex Co‐Delivering Photosensitizer and TLR7/8 Agonist to Trigger Effective Anti‐Tumor Immune Responses
Yutong Liu, Hui Li, Huajun Zhao, Yanyun Hao, Simon Van Herck, Zejun Xu, Guan Wang, Xiao Wang, Xinke Zhang, Xiaoyan Ge, Xia Li, Ailu Yang, Hongfei Chen, Jing Zou, Wentao Wang, Bruno G. De Geest, Zhiyue Zhang
Abstract
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.