Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells

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  • 作者:Shi Jiaqi, Wu Wei, Chen Dong, Liao Ziyan, Sheng Tao, Wang Yanfang, Yao Yuejun, Wu Qing, Liu Feng, Zhou Ruyi, Zhu Chaojie, Shen Xinyuan, Mao Zhengwei, Ding Yuan, Wang Weilin, Dotti Gianpietro, Sun Jie, Liang Xiao, Fang Weijia, Zhao Peng, Li Hongjun, Gu Zhen
  • 期刊:NATURE MATERIALS
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Lymph nodes are crucial organs of the adaptive immune system, orchestrating T cell priming, activation and tolerance. T cell activity and function are highly regulated by lymph nodes, which have a unique structure harbouring distinct cells that work together to detect and respond to pathogen-derived antigens. Here we show that implanted patient-derived freeze-dried lymph nodes loaded with chimeric antigen receptor T cells improve delivery to solid tumours and inhibit tumour recurrence after surgery. Chimeric antigen receptor T cells can be effectively loaded into lyophilized lymph nodes, whose unaltered meshwork and cytokine and chemokine contents promote chimeric antigen receptor T cell viability and activation. In mouse models of cell-line-derived human cervical cancer and patient-derived pancreatic cancer, delivery of chimeric antigen receptor T cells targeting mesothelin via the freeze-dried lymph nodes is more effective in preventing tumour recurrence when compared to hydrogels containing T-cell-supporting cytokines. This tissue-mediated cell delivery strategy holds promise for controlled release of various cells and therapeutics with long-term activity and augmented function.

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