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Simultaneous targeting of primary tumor, draining lymph node, and distant metastases through high endothelial venule-targeted delivery

Abstract : Cancer patients with malignant involvement of tumor-draining lymph nodes (TDLNs) and distant metastases have the poorest prognosis. A drug delivery platform that targets the primary tumor, TDLNs, and metastatic niches simultaneously, remains to be developed. Here, we generated a novel monoclonal antibody (MHA112) against peripheral node addressin (PNAd), a family of glycoproteins expressed on high endothelial venules (HEVs), which are present constitutively in the lymph nodes (LNs) and formed ectopically in the tumor stroma. MHA112 was endocytosed by PNAd-expressing cells, where it passed through the lysosomes. MHA112 conjugated antineoplastic drug Paclitaxel (Taxol) (MHA112-Taxol) delivered Taxol effectively to the HEV-containing tumors, TDLNs, and metastatic lesions. MHA112-Taxol treatment significantly reduced primary tumor size as well as metastatic lesions in a number of mouse and human tumor xenografts tested. These data indicate that human metastatic lesions contain HEVs and provide a platform that permits simultaneous targeted delivery of antineoplastic drugs to the three key sites of primary tumor, TDLNs, and metastases.
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https://hal.univ-lille.fr/hal-03153047
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Soumis le : vendredi 26 février 2021 - 08:50:36
Dernière modification le : vendredi 1 avril 2022 - 03:52:46

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Liwei Jiang, Sungwook Jung, Jing Zhao, Vivek Kasinath, Takaharu Ichimura, et al.. Simultaneous targeting of primary tumor, draining lymph node, and distant metastases through high endothelial venule-targeted delivery. Nano Today, Elsevier, 2021, Nano Today, 36, pp.101045. ⟨10.1016/j.nantod.2020.101045⟩. ⟨hal-03153047⟩

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