An improved cell line-derived xenograft humanized mouse model for evaluation of PD-1/PD-L1 blocker BMS202-induced immune responses in colorectal cancer

Zhang, Wanheng; Shang, Pengzhao; Yu, Liting; Cao, Shucheng; Guo, Cheng

doi:10.3724/abbs.2022145

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…Especially, the nature of poor conservation of intronic sequences and minimal overlap of mis-spliced transcripts between mice and humans ( Lieu et al, 2022 ) suggest that mice may be less useful in modeling patients with AS dysregulation. Last, it is complex and time-consuming to manipulate genes in mice by multigenerational hybridization, which may result in patients missing optimal treatment periods ( Shang et al, 2022 ; Stribbling and Ryan, 2022 ). Recent studies have shown that organoids are highly effective in disease modeling and are widely utilized for basic research, drug selection and personalized medicine, which may also benefit the splicing-targeted immunotherapies ( Drost and Clevers, 2018 ).…”

Section: Sectionmentioning

confidence: 99%

Targeting alternative splicing in cancer immunotherapy

Han

Liu

2023

Front. Cell Dev. Biol.

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Tumor immunotherapy has made great progress in cancer treatment but still faces several challenges, such as a limited number of targetable antigens and varying responses among patients. Alternative splicing (AS) is an essential process for the maturation of nearly all mammalian mRNAs. Recent studies show that AS contributes to expanding cancer-specific antigens and modulating immunogenicity, making it a promising solution to the above challenges. The organoid technology preserves the individual immune microenvironment and reduces the time/economic costs of the experiment model, facilitating the development of splicing-based immunotherapy. Here, we summarize three critical roles of AS in immunotherapy: resources for generating neoantigens, targets for immune-therapeutic modulation, and biomarkers to guide immunotherapy options. Subsequently, we highlight the benefits of adopting organoids to develop AS-based immunotherapies. Finally, we discuss the current challenges in studying AS-based immunotherapy in terms of existing bioinformatics algorithms and biological technologies.

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Section: Sectionmentioning

confidence: 99%

Targeting alternative splicing in cancer immunotherapy

Han

Liu

2023

Front. Cell Dev. Biol.

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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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Effect of colorectal cancer stem cells on the development and metastasis of colorectal cancer

Deng,

Zheng,

et al. 2024

World J Gastrointest Oncol

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The relevant mechanism of tumor-associated macrophages (TAMs) in the treatment of colorectal cancer patients with immune checkpoint inhibitors (ICIs) is discussed, and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies. As a class of drugs widely used in clinical tumor immunotherapy, ICIs can act on regulatory molecules on cells that play an inhibitory role - immune checkpoints - and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system. The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly. The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs. ICIs can regulate the phenotypic function of TAMs, and TAMs can also affect the tolerance of colorectal cancer to ICI therapy. TAMs play an important role in ICI resistance, and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

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An improved cell line-derived xenograft humanized mouse model for evaluation of PD-1/PD-L1 blocker BMS202-induced immune responses in colorectal cancer

Cited by 3 publications

References 43 publications

Targeting alternative splicing in cancer immunotherapy

Targeting alternative splicing in cancer immunotherapy

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

Effect of colorectal cancer stem cells on the development and metastasis of colorectal cancer

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