Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response

Xiang Yu, Yanfeng Dai, Yifan Zhao, Shuhong Qi, Lei Liu, Lisen Lu, Qingming Luo and Zhihong Zhang ()
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Xiang Yu: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Yanfeng Dai: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Yifan Zhao: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Shuhong Qi: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Lei Liu: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Lisen Lu: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Qingming Luo: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology
Zhihong Zhang: Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Targeted delivery of a nanovaccine loaded with a tumor antigen and adjuvant to the lymph nodes (LNs) is an attractive approach for improving cancer immunotherapy outcomes. However, the application of this technique is restricted by the paucity of suitable tumor-associated antigens (TAAs) and the sophisticated technology required to identify tumor neoantigens. Here, we demonstrate that a self-assembling melittin-lipid nanoparticle (α-melittin-NP) that is not loaded with extra tumor antigens promotes whole tumor antigen release in situ and results in the activation of antigen-presenting cells (APCs) in LNs. Compared with free melittin, α-melittin-NPs markedly enhance LN accumulation and activation of APCs, leading to a 3.6-fold increase in antigen-specific CD8+ T cell responses. Furthermore, in a bilateral flank B16F10 tumor model, primary and distant tumor growth are significantly inhibited by α-melittin-NPs, with an inhibition rate of 95% and 92%, respectively. Thus, α-melittin-NPs induce a systemic anti-tumor response serving as an effective LN-targeted whole-cell nanovaccine.

Date: 2020
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DOI: 10.1038/s41467-020-14906-9

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