Mannose modified co-loaded zoledronic liposomes deplete M2-tumor-associated macrophages to enhance anti-tumor effect of doxorubicin on TNBC

Wendong, Yao; Hengwu, Xu; Chen, Yanhong; Xu, Yingying; Zhu, Feng; Zeng, Wang; Cai, Xiaoxiao

doi:10.1016/j.jddst.2022.103551

Cited by 3 publications

(2 citation statements)

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“…Anti‐tumour efficacy that has been observed in mouse models that lack γδ T cells has been suggested to be a result of endocytosis of n‐BPs by TAMs, as n‐BPs have been shown to cause the depletion of these cells 66,88 . In hepatocellular carcinoma and triple‐negative breast cancer xenograft mouse models, liposomal ZOL was shown to eliminate both M1 anti‐tumoral and M2 pro‐tumoral TAMs, favouring elimination of M2 macrophages, although this was attributed to the ratio of M1:M2 TAMs in the tumour models used 89,90 . Adoptive immunotherapy using Vγ9Vδ2 T cells activated by liposomal ALD has been demonstrated to be efficacious in the treatment of epithelial ovarian cancer in mice 91 .…”

Section: Future Directions For Clinical Translationmentioning

confidence: 99%

“… 66 , 88 In hepatocellular carcinoma and triple‐negative breast cancer xenograft mouse models, liposomal ZOL was shown to eliminate both M1 anti‐tumoral and M2 pro‐tumoral TAMs, favouring elimination of M2 macrophages, although this was attributed to the ratio of M1:M2 TAMs in the tumour models used. 89 , 90 Adoptive immunotherapy using Vγ9Vδ2 T cells activated by liposomal ALD has been demonstrated to be efficacious in the treatment of epithelial ovarian cancer in mice. 91 Lipid‐based nanocarrier approaches have shown extensive efficacy in the activation of γδ T‐cell‐mediated lysis against cancer cells in vitro and in mouse models yet there are still toxicity and bioavailability issues that must be addressed to achieve clinical efficacy.…”

Section: Future Directions For Clinical Translationmentioning

confidence: 99%

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Effective γδ T‐cell clinical therapies: current limitations and future perspectives for cancer immunotherapy

Revesz,

Joyce,

Ebert

et al. 2024

Clin & Trans Imm

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Abstractγδ T cells are a unique subset of T lymphocytes, exhibiting features of both innate and adaptive immune cells and are involved with cancer immunosurveillance. They present an attractive alternative to conventional T cell‐based immunotherapy due, in large part, to their lack of major histocompatibility (MHC) restriction and ability to secrete high levels of cytokines with well‐known anti‐tumour functions. To date, clinical trials using γδ T cell‐based immunotherapy for a range of haematological and solid cancers have yielded limited success compared with in vitro studies. This inability to translate the efficacy of γδ T‐cell therapies from preclinical to clinical trials is attributed to a combination of several factors, e.g. γδ T‐cell agonists that are commonly used to stimulate populations of these cells have limited cellular uptake yet rely on intracellular mechanisms; administered γδ T cells display low levels of tumour‐infiltration; and there is a gap in the understanding of γδ T‐cell inhibitory receptors. This review explores the discrepancy between γδ T‐cell clinical and preclinical performance and offers viable avenues to overcome these obstacles. Using more direct γδ T‐cell agonists, encapsulating these agonists into lipid nanocarriers to improve their pharmacokinetic and pharmacodynamic profiles and the use of combination therapies to overcome checkpoint inhibition and T‐cell exhaustion are ways to bridge the gap between preclinical and clinical success. Given the ability to overcome these limitations, the development of a more targeted γδ T‐cell agonist‐checkpoint blockade combination therapy has the potential for success in clinical trials which has to date remained elusive.

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Section: Future Directions For Clinical Translationmentioning

confidence: 99%