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Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer.
Ou, Da-Liang; Liao, Zi-Xian; Kempson, Ivan M; Li, Lin; Yang, Pan-Chyr; Tseng, S-Ja.
Afiliación
  • Ou DL; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, 10051, Taiwan.
  • Liao ZX; National Taiwan University YongLin Institute of Health, National Taiwan University, Taipei, 10051, Taiwan.
  • Kempson IM; Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan.
  • Li L; Future Industries Institute, University of South Australia, Mawson Lakes, SA, 5095, Australia.
  • Yang PC; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, 10051, Taiwan.
  • Tseng SJ; Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, 10051, Taiwan. pcyang@ntu.edu.tw.
J Biomed Sci ; 31(1): 1, 2024 Jan 02.
Article en En | MEDLINE | ID: mdl-38163894
ABSTRACT

BACKGROUND:

As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with other therapies has shown promising results for treating unresectable HCC, offering new opportunities. Recombinant adeno-associated viral type 2 (AAV2) virotherapy has been approved for clinical use but it efficacy is stifled through systemic administration. On the other hand, iron oxide nanoparticles (ION) can be cleared via the liver and enhance macrophage polarization, promoting infiltration of CD8+ T cells and creating a more favorable tumor microenvironment for immunotherapy.

METHODS:

To enhance the efficacy of virotherapy and promote macrophage polarization towards the M1-type in the liver, ION-AAV2 were prepared through the coupling of ION-carboxyl and AAV2-amine using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (Sulfo-NHS). Efficacy after systemic delivery of ION-AAV2 in an orthotopic HCC model was evaluated.

RESULTS:

After 28 days, the tumor weight in mice treated with ION-AAV2 was significantly reduced by 0.56-fold compared to the control group. The ION-AAV2 treatment led to an approximate 1.80-fold increase in the level of tumor associated M1-type macrophages, while the number of M2-type macrophages was reduced by 0.88-fold. Moreover, a proinflammatory response increased the population of tumor-infiltrating CD8+ T cells in the ION-AAV2 group. This transformation converted cold tumors into hot tumors.

CONCLUSIONS:

Our findings suggest that the conjugation of ION with AAV2 could be utilized in virotherapy while simultaneously exploiting macrophage-modulating cancer immunotherapies to effectively suppress HCC growth.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Biomed Sci Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Biomed Sci Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido