131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer

Liu, Na; He, Tiantian; Xiao, Zewei; Du, Juan; Zhu, Keke; Liu, Xiongying; Chen, Tongsheng; Liu, Wenjuan; Ni, Guoying; Liu, Xiaosong; Wang, Tianfang; Quan, Jiangtao; Zhang, Jinhe; Zhang, Peipei; Yuan, Jing

doi:10.3389/fonc.2022.861206

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Caerin 1.1/1.9 peptides are able to inhibit the proliferation of TC-1 [ 24 , 25 ], HeLa [ 26 ] and A549 [ 27 ] cells in vitro, and induce cell apoptosis, probably through the stimulation of the TNF-α signalling pathway [ 26 , 28 ]. Caerin 1.1/1.9 inhibited TC-1 tumour growth and modified the functions of tumour infiltrating immune cells, such as T cells, NK cells, and dendritic cells in vivo [ 23 , 29 ], and more activated CD8+ T cells and NK cells were recruited to the tumour sites [ 23 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Caerin 1.1/1.9 Enhances Antitumour Immunity by Activating the IFN-α Response Signalling Pathway of Tumour Macrophages

Yang

Liu

et al. 2022

Cancers

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Macrophages are one of the essential components of the tumour microenvironment (TME) of many cancers and show complex heterogeneity and functions. More recent research has been focusing on the characterisation of tumour-associated macrophages (TAMs). Previously, our study demonstrated that caerin 1.1/1.9 peptides significantly improve the therapeutic efficacy of combined specific immunotherapy and immune checkpoint blockade in a murine transplantable tumour model (TC-1). In this study, the mice inoculated with TC-1 tumour were immunised differently. The TAMs were isolated using flow cytometry and characterised by cytokine ELISA. The survival rates of mice with different treatments containing caerin 1.1/19 were assessed comparatively, including those with/without macrophage depletion. The single-cell RNA sequencing (scRNA-seq) data of previous studies were integrated to further reveal the functions of TAMs with the treatments containing caerin 1.1/1.9. As a comparison, the TAMs of stage I and II cervical cancer patients were analysed using scRNA-seq analysis. We demonstrate that caerin induced tumour clearance is associated with infiltration of tumours by IL-12 secreting Ly6C+F4/80+ macrophages exhibiting enhanced IFN-α response signalling, renders animals resistant to further tumour challenge, which is lost after macrophage depletion. Our results indicate that caerin 1.1/1.9 treatment has great potential in improving current immunotherapy efficacy.

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Section: Introductionmentioning

confidence: 99%

Caerin 1.1/1.9 Enhances Antitumour Immunity by Activating the IFN-α Response Signalling Pathway of Tumour Macrophages

Yang

Liu

et al. 2022

Cancers

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“…It has been shown that the mixture containing caerin 1.1 and caerin 1.9 with an equal molar ratio (caerin 1.1/1.9, synthesised and simpli ed as F1/F3) can inhibit the growth of human and mouse cervical cancer cells, human thyroid cancer cells, and human breast cancer cells in vitro, and induce apoptosis in HeLa cells, probably through the TNFα signalling pathway, with an additive effect [21][22][23]. Coupling these peptides with nuclide can improve their anti-tumour e ciency [24]. Furthermore, F1/F3 can inhibit the growth of TC-1 cells in vivo and attract immune cells, such as T cells and NK cells, to the tumour tissue [25].…”

mentioning

confidence: 99%

Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine of IFNα and is enhanced by CD47 blockade

Li,

Luo,

et al. 2023

Preprint

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Background Immunotherapy has greatly changed the landscape of cancer therapy; however, only a subset of patients responds to immune checkpoint blockade or to CAR-T based therapy. Previously, we demonstrated that natural host-defence peptide caerin1.1/caerin1.9 (F1/F3) increases the efficacy of anti-PD-1 and therapeutic vaccine, in a HPV16 + TC-1 tumour model, but the anti-tumor mechanism of F1/F3 is still unclear. Methods In this study, we explored the impact of F1/F3 on the tumor microenvironment in a transplanted B16 melanoma model, and further investigated the mechanism of action of F1/F3 using monoclonal antibodies to deplete relevant cells, gene knockout mice and flow cytometry. Results we show that F1/F3 is able to inhibit the growth of melanoma B16 tumour cells both in vitro and in vivo. Depletion of macrophages, blockade of IFNα receptor, and Stat1 inhibition each abolishes F1/F3-mediated antitumor responses. Subsequent analysis reveals that F1/F3 increases the tumour infiltration of inflammatory macrophages, upregulates the expression of IFNα receptor, and promotes the secretion of IFNα by macrophages. Interestingly, F1/F3 upregulates CD47 expression on tumour cells; and blocking CD47 increases F1/F3-mediated antitumor responses. Furthermore, F1/F3 intratumor injection, CD47 blockade, and therapeutic vaccination significantly increases the survival time of B16 tumour-bearing mice. These results indicate that F1/F3 may be effective to improve the efficacy of ICB and therapeutic vaccine-based immunotherapy for human epithelial cancers and warrants consideration for clinical trials.

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Caerin 1.1 and 1.9 peptides halt B16 melanoma metastatic tumours via expanding cDC1 and reprogramming tumour macrophages

Fu,

Luo,

et al. 2024

Preprint

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Background Cancer immunotherapy, particularly immune checkpoint inhibitors (ICBs) such as anti-PD-1 antibodies, has revolutionized cancer treatment, although response rates vary among patients. Previous studies have demonstrated that caerin 1.1 and 1.9, host-defence peptides from the Australian tree frog, enhance the effectiveness of anti-PD-1 and therapeutic vaccines in a murine TC-1 model by activating tumour-associated macrophages intratumorally. Methods We employed a murine B16 melanoma model to investigate the therapeutic potential of caerin 1.1 and 1.9 in combination with anti-CD47 and a therapeutic vaccine (triple therapy, TT). Tumour growth of caerin-injected primary tumours and distant metastatic tumours was assessed, and survival analysis conducted. Single-cell RNA sequencing (scRNAseq) of CD45+ cells isolated from distant tumours was performed to elucidate changes in the tumour microenvironment induced by TT. Results The TT treatment significantly reduced tumour volumes on the treated side compared to untreated and control groups, with notable effects observed by Day 21. Survival analysis indicated extended survival in mice receiving TT, both on the treated and distant sides. scRNAseq revealed a notable expansion of conventional type 1 dendritic cells (cDC1s) and CD4+CD8+ T cells in the TT group. Tumour-associated macrophages in the TT group shifted toward a more immune-responsive M1 phenotype, with enhanced communication observed between cDC1s and CD8+ and CD4+CD25+ T cells. Additionally, TT downregulated M2-like macrophage marker genes, particularly in MHCIIhi and tissue-resident macrophages, suppressing Cd68 and Arg1 expression across all macrophage types. Differential gene expression analysis highlighted pathway alterations, including upregulation of oxidative phosphorylation and MYC target V1 in Arg1hi macrophages, and activation of pro-inflammatory pathways in MHCIIhi and tissue-resident macrophages. Conclusion Our findings suggest that caerin 1.1 and 1.9, combined with immunotherapy, effectively modulate the tumour microenvironment in primary and secondary tumours, leading to reduced tumour growth and enhanced systemic immunity. Further investigation into these mechanisms could pave the way for improved combination therapies in advanced melanoma treatment.

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131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer

Cited by 3 publications

References 36 publications

Caerin 1.1/1.9 Enhances Antitumour Immunity by Activating the IFN-α Response Signalling Pathway of Tumour Macrophages

Caerin 1.1/1.9 Enhances Antitumour Immunity by Activating the IFN-α Response Signalling Pathway of Tumour Macrophages

Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine of IFNα and is enhanced by CD47 blockade

Caerin 1.1 and 1.9 peptides halt B16 melanoma metastatic tumours via expanding cDC1 and reprogramming tumour macrophages

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