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 ALDH 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 ALDH CSCs. Nanodiscs increased antigen trafficking to lymph nodes and generated robust ALDH-specific T cell responses. Nanodisc vaccination against ALDH 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.
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http://dx.doi.org/10.1021/acs.nanolett.0c03414 | DOI Listing |
Cells
December 2024
Translational Medicine, School of Science, Engineering and Environment (SEE), University of Salford, Greater Manchester, Salford M5 4WT, UK.
Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epithelial-mesenchymal transition (EMT), a dynamic process involved in reprogramming cancer cells towards a more aggressive and motile phenotype with increased stemness potential.
View Article and Find Full Text PDFSAR QSAR Environ Res
October 2024
Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Kingdom of Saudi Arabia.
Human aldehyde dehydrogenases (ALDHs) are a group of 19 isoforms often overexpressed in cancer stem cells (CSCs). These enzymes play critical roles in CSC protection, maintenance, cancer progression, therapeutic resistance, and poor prognosis. Thus, targeting ALDH isoforms offers potential for innovative cancer treatments.
View Article and Find Full Text PDFJ Transl Med
October 2024
Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Ann Med Surg (Lond)
October 2024
Department of Radiotherapy of the Fifth Clinical Medical College of Shanxi Medical University, People's Hospital of Shanxi Province, Taiyuan, Shanxi.
Radiotherapy is widely regarded as the primary therapeutic modality for nasopharyngeal cancer (NPC). Studies have shown that cancer cells with high resistance to radiation, known as radioresistant cancer cells, may cause residual illness, which in turn might contribute to the occurrence of cancer recurrence and metastasis. It has been shown that cancer stem-like cells (CSCs) exhibit resistance to radiation therapy.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 2024
Serviço de Biologia Celular, Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias - Rua Conde Pereira Carneiro 80, Gameleira, Belo Horizonte, Minas Gerais, 30510-010, Brazil.
Triple-negative breast cancer is a heterogeneous disease with high recurrence and mortality, linked to cancer stem cells (CSCs). Our study characterized distinct cell subpopulations and signaling pathways to explore chemoresistance. We observed cellular heterogeneity among and within the cells regarding phenotyping and drug response.
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