In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases

https://doi.org/10.1016/j.apsb.2024.06.003

This new article publication from Acta Pharmaceutica Sinica B, discusses the use of in situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases.

Tumor vaccine, a promising modality of tumor immunotherapy, needs to go through the process of tumor antigen generation and loading, antigen drainage to lymph nodes (LNs), antigen internalization by dendritic cells (DCs), DC maturation, and antigen cross-presentation to activate T-cells. However, tumor vaccines are often unable to satisfy all the steps, leading to the limitation of their application and efficacy.

This article describes, based on a smart nanogel system, how an in situ nano-vaccine (CpG@Man-P/Tra/Gel) targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer. The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib (Tra) and nano-adjuvant CPG@Man-P, which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P. Benefiting from mannose (Man) modification, the nano-vaccines targeted to LNs, promoted the uptake of antigens by DCs, further inducing the maturation of DCs and activation of T cells. Moreover, CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.

Notably, combined with PD-1 blocking, the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

Keywords: In situ nano-vaccine, Lymph node targeting, MMP-2 responsive, PD-1, Combination therapy, CpG, Ovarian cancer, Metastases

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S221138352400234X-ga1_lrg.jpg

A smart tumor in situ nano-vaccine Tra/CpG@Man-P/Gel was constructed, and the size of nanoadjuvants was optimixed, to induce potent antitumor immunity and inhibit the primary and metastatic tumors.

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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

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CiteScore: 22.4

Impact Factor: 14.7 (Top 5 journal in the category of Pharmacology and pharmacy)

JIF without self-citation: 13.9

ISSN 2211-3835

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Yuan Li, Fan Tong, Yufan Wang, Jing Wang, Manqi Wu, Hanmei Li, Hongyan Guo, Huile Gao,, In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases, Acta Pharmaceutica Sinica B, Volume 14, Issue 9, 2024, Pages 4102-4117, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2024.06.003