Combined therapeutic effect of YHO-1701 with PD-1 blockade is dependent on natural killer cell activity in syngeneic mouse models

Takahashi, Hiroyuki; Miyoshi, Nao; Murakami, Hisashi; Okamura, Yuki; Ogo, Naohisa; Takagi, Akimitsu; Muraoka, Daisuke; Asai, Akira

doi:10.1007/s00262-023-03440-4

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…Strategies to inhibit the JAKs/STAT3 pathway prove instrumental in mitigating immune tolerance in cancer cells, with tangible outcomes observed in restraining tumor invasion and growth in xenografts (52,54,62). The confirmation of the pathway's crucial role in cancer immune tolerance underscores its potential as a therapeutic target, offering prospects for novel interventions in the complex landscape of cancer biology.…”

Section: Jaks-stat3 Signaling Pathwaymentioning

confidence: 99%

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Gan,

Li,

et al. 2024

Front. Immunol.

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Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy’s evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer’s immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.

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Section: Jaks-stat3 Signaling Pathwaymentioning

confidence: 99%

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Gan,

Li,

et al. 2024

Front. Immunol.

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BP1003 Decreases STAT3 Expression and Its Pro-Tumorigenic Functions in Solid Tumors and the Tumor Microenvironment

Gagliardi,

Kean,

Dai

et al. 2024

Biomedicines

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Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2+, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in vivo patient-derived models of pancreatic ductal adenocarcinoma (PDAC) show reduced tissue viability and tumor volume with BP1003 and gemcitabine combination treatments. In addition to directly affecting tumor cells, BP1003 can modulate the tumor microenvironment. Unlike M1 differentiation, monocyte differentiation into anti-inflammatory M2 macrophages is suppressed by BP1003, indicating its potential contribution to immunotherapy. The broad anti-tumor effect of BP1003 in numerous preclinical solid tumor models, such as breast, ovarian, and pancreatic cancer models shown in this work, makes it a promising cancer therapeutic.

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Combined therapeutic effect of YHO-1701 with PD-1 blockade is dependent on natural killer cell activity in syngeneic mouse models

Cited by 2 publications

References 39 publications

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

BP1003 Decreases STAT3 Expression and Its Pro-Tumorigenic Functions in Solid Tumors and the Tumor Microenvironment

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