Enhanced chemoimmunotherapy of breast cancer in mice by apolipoprotein A1-modified doxorubicin liposomes combined with interleukin-21.
J Drug Target
; 31(10): 1098-1110, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37909691
ABSTRACT
Backgroud Breast cancer is a prevalent malignancy among women, with triple-negative breast cancer (TNBC) comprising approximately 15-20% of all cases, possessing high invasiveness, drug resistance and poor prognosis. Chemotherapy, the main treatment for TNBC, is limited by toxicity and drug resistance. Apolipoprotein A1 modified doxorubicin liposome (ApoA1-lip/Dox) was constructed in our previous study, with promising anti-tumour effect and improved safety been proved. However, during long-term administration, the problem of cumulative toxicity and insufficient tumour inhibition is still inevitable. Interleukin-21 is a small molecule protein secreted by T cells with various immune regulatory functions. IL-21 has significantly curative effects in numerous solid tumours, but it has the disadvantages of low response rate and short half-life. The combination of chemotherapy and immunotherapy has received increasing attention.Purpose:
In this study, ApoA1 drug loading system and long-acting IL-21 are innovatively combined for tumour treatment.Methods:
We combined ApoA1-lip/Dox and IL-21 for treatment and evaluated their impact on tumor-infiltrating lymphocytes and CD8+ T and NK cell cytotoxicity.Results:
Combined administration significantly improved the tumour-infiltrating lymphocytes and enhanced the cytotoxicity of CD8+ T and NK cells. The combination of ApoA1-lip/Dox and IL-21 exhibits significantly enhanced anti-tumour efficacy with lower toxicity of ApoA1-lip/Dox, providing a new strategy for TNBC treatment with enhanced anti-tumour response and reduced toxicity.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
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Lipossomos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article