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MDSC-targeted liposomal all-trans retinoic acid suppresses mMdscs and improves immunotherapy in HBV infection.
Kesse, Samuel; Xu, Yuhong; Shi, Sanyuan; Jin, Shanshan; Ullah, Shafi; Dai, Yongchao; He, Miao; Zheng, Anjie; Xu, Fengwei; Du, Zixiu; Alolga, Raphael N; Peng, Jinliang.
Afiliación
  • Kesse S; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
  • Xu Y; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
  • Shi S; Yunnan Key Laboratory of Screening and Research on Anti-pathogen Plant Resources in Western Yunnan, Dali University, Dali, China.
  • Jin S; HighField Biopharmaceuticals Inc, Hangzhou, China.
  • Ullah S; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
  • Dai Y; HighField Biopharmaceuticals Inc, Hangzhou, China.
  • He M; Shanghai Institute of Digestive Diseases, Renji Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zheng A; HighField Biopharmaceuticals Inc, Hangzhou, China.
  • Xu F; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
  • Du Z; Yunnan Key Laboratory of Screening and Research on Anti-pathogen Plant Resources in Western Yunnan, Dali University, Dali, China.
  • Alolga RN; HighField Biopharmaceuticals Inc, Hangzhou, China.
  • Peng J; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Expert Opin Drug Deliv ; 21(2): 347-363, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38406829
ABSTRACT

BACKGROUND:

Myeloid-derived suppressor cells (MDSCs) are evolving as a prominent determinant in cancer occurrence and development and are functionally found to suppress T cells in cancer. Not much research is done regarding its involvement in viral infections. This research was designed to investigate the role of MDSCs in hepatitis B virus (HBV) infection and how targeting these cells with our novel all-trans retinoic acid encapsulated liposomal formulation could improve immunotherapy in C57BL/6 mice.

METHODS:

Ten micrograms (10 µg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily.

RESULTS:

Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF.

CONCLUSIONS:

In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis B Crónica / Células Supresoras de Origen Mieloide / Hepatitis B / Neoplasias Límite: Animals Idioma: En Revista: Expert Opin Drug Deliv Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis B Crónica / Células Supresoras de Origen Mieloide / Hepatitis B / Neoplasias Límite: Animals Idioma: En Revista: Expert Opin Drug Deliv Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido