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Article Dans Une Revue Nano Today Année : 2021

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

Jing Zhao
  • Fonction : Auteur
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Andrew S Liss
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Nasim Annabi
Nitin Joshi
Tomoya O Akama
Jonathan S Bromberg
  • Fonction : Auteur
Motohiro Kobayashi
Reza Abdi
  • Fonction : Auteur

Résumé

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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Dates et versions

hal-03445338 , version 1 (23-11-2021)

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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, 2021, 36, ⟨10.1016/j.nantod.2020.101045⟩. ⟨hal-03445338⟩

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