Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Li, Yan-Ruide; Zhou, Yang; Wilson, Matthew; Kramer, Adam; Hon, Ryan; Zhu, Yichen; Fang, Ying; Yang, Lili

doi:10.3390/ijms23147547

Cited by 7 publications

(5 citation statements)

References 47 publications

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“…However, the production of IFN-γ by iNKT and other lymphocytes was essential for protection. Using humanised NSG mice, a recent study showed that tumour localised administration of αGalCer can significantly enhance iNKT cell-mediated anti-tumour capacity against solid tumours ( 75 ).…”

Section: Preclinical Studies: Inkt Cells In Cancermentioning

confidence: 99%

Towards a better understanding of human iNKT cell subpopulations for improved clinical outcomes

et al. 2023

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Invariant natural killer T (iNKT) cells are a unique T lymphocyte population expressing semi-invariant T cell receptors (TCRs) that recognise lipid antigens presented by CD1d. iNKT cells exhibit potent anti-tumour activity through direct killing mechanisms and indirectly through triggering the activation of other anti-tumour immune cells. Because of their ability to induce potent anti-tumour responses, particularly when activated by the strong iNKT agonist αGalCer, they have been the subject of intense research to harness iNKT cell-targeted immunotherapies for cancer treatment. However, despite potent anti-tumour efficacy in pre-clinical models, the translation of iNKT cell immunotherapy into human cancer patients has been less successful. This review provides an overview of iNKT cell biology and why they are of interest within the context of cancer immunology. We focus on the iNKT anti-tumour response, the seminal studies that first reported iNKT cytotoxicity, their anti-tumour mechanisms, and the various described subsets within the iNKT cell repertoire. Finally, we discuss several barriers to the successful utilisation of iNKT cells in human cancer immunotherapy, what is required for a better understanding of human iNKT cells, and the future perspectives facilitating their exploitation for improved clinical outcomes.

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Section: Preclinical Studies: Inkt Cells In Cancermentioning

confidence: 99%

Towards a better understanding of human iNKT cell subpopulations for improved clinical outcomes

et al. 2023

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“…Recent investigations have included the application of human iNKT cells transferred to humanized mice with tumors, along with direct α-GalCer administration into these tumors. These studies revealed a robust and rapid recruitment of iNKT cells, resulting in effective anti-tumor effects [203].…”

Section: Current Advances In Inkt-mediated Cancer Immunotherapymentioning

confidence: 99%

Natural Killer T Cell Diversity and Immunotherapy

Tognarelli,

Gutiérrez-Vera,

Palacios

et al. 2023

Cancers

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Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

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“…Human invariant natural killer T (iNKT) cells treated with α‐GalCer showed significantly increased efficacy in tumor‐bearing NSG mice, but the dose of α‐GalCer was related to the efficacy and safety of iNKT cell therapy (Y.‐R. Li et al, 2022). Furthermore, blocking the functional C–C'loop region of a V‐domain Ig suppressor of T‐cell activation to reduce inhibition of myeloid‐derived T cell activity and prevented neutrophil migration (Thakkar et al, 2022).…”

Section: Cancer Treatment Based On Humanized Micementioning

confidence: 99%

“…. Human invariant natural killer T (iNKT) cells treated with α-GalCer showed significantly increased efficacy in tumor-bearing NSG mice, but the dose of α-GalCer was related to the efficacy and safety of iNKT cell therapy (Y.-R Li et al, 2022)(Thakkar et al, 2022).…”

mentioning

confidence: 99%

Humanized mouse models: A valuable platform for preclinical evaluation of human cancer

Yang,

Li,

et al. 2023

Biotech & Bioengineering

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Animal models are routinely employed to assess the treatments for human cancer. However, due to significant differences in genetic backgrounds, traditional animal models are unable to meet bioresearch needs. To overcome this restriction, researchers have generated and optimized immunodeficient mice, and then engrafted human genes, cells, tissues, or organs in mice so that the responses in the model mice could provide a more reliable reference for treatments. As a bridge connecting clinical application and basic research, humanized mice are increasingly used in the preclinical evaluation of cancer treatments, particularly after gene interleukin 2 receptor gamma mutant mice were generated. Human cancer models established in humanized mice support exploration of the mechanism of cancer occurrence and provide an efficient platform for drug screening. However, it is undeniable that the further application of humanized mice still faces multiple challenges. This review summarizes the construction approaches for humanized mice and their existing limitations. We also report the latest applications of humanized mice in preclinical evaluation for the treatment of cancer and point out directions for future optimization of these models.

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Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Cited by 7 publications

References 47 publications

Towards a better understanding of human iNKT cell subpopulations for improved clinical outcomes

Towards a better understanding of human iNKT cell subpopulations for improved clinical outcomes

Natural Killer T Cell Diversity and Immunotherapy

Humanized mouse models: A valuable platform for preclinical evaluation of human cancer

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