| Literature DB >> 32926633 |
Alireza Hassani Najafabadi1,2, Jing Zhang3,4, Marisa E Aikins1,2, Zeynab Izadi Najaf Abadi1,2, Fei Liao3,5, You Qin3,6, Emeka B Okeke1,2, Lindsay M Scheetz1,2, Jutaek Nam1,2, Yao Xu1,2, David Adams7, Patrick Lester8, Taryn Hetrick8, Anna Schwendeman1,2, Max S Wicha3, Alfred E Chang3, Qiao Li3, James J Moon1,2,9.
Abstract
Cancer stem cells (CSCs) proliferate extensively and drive tumor metastasis and recurrence. CSCs have been identified in over 20 cancer types to date, but it remains unknown how to target and eliminate CSCs in vivo. Aldehyde dehydrogenase (ALDH) is a marker that has been used extensively for isolating CSCs. Here we present a novel approach to target and reduce the frequency of ALDHhigh CSCs by vaccination against ALDH. We have identified ALDH1-A1 and ALDH1-A3 epitopes from CSCs and developed synthetic high-density lipoprotein nanodiscs for vaccination against ALDHhigh CSCs. Nanodiscs increased antigen trafficking to lymph nodes and generated robust ALDH-specific T cell responses. Nanodisc vaccination against ALDHhigh CSCs combined with anti-PD-L1 therapy exerted potent antitumor efficacy and prolonged animal survival in multiple murine models. Overall, this is the first demonstration of a simple nanovaccine strategy against CSCs and may lead to new avenues for cancer immunotherapy against CSCs.Entities:
Keywords: Cancer stem cells; aldehyde dehydrogenase; breast cancer; cancer vaccine; melanoma
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Year: 2020 PMID： 32926633 PMCID： PMC7572838 DOI： 10.1021/acs.nanolett.0c03414
Source DB: PubMed Journal: Nano Lett ISSN： 1530-6984 Impact factor: 11.189