IL-11Rα-targeted nanostrategy empowers chemotherapy of relapsed and patient-derived osteosarcoma

Jiang, Jingjing; Wang, Renxian; Yang, Liang; Sha, Yongjie; Zhao, Songsong; Guo, Jianxun; Chen, Dafu; Zhong, Zhiyuan; Meng, Fenghua

doi:10.1016/j.jconrel.2022.08.048

Cited by 7 publications

(8 citation statements)

References 39 publications

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“…Adding substance to this theory, the research by Jiang et al [ 130 ] delves deep into the applicability of redox-responsive polymersomes in osteosarcoma therapy. They championed the IL11-PDOX nanosystem—a redox-responsive polymersome loaded with the potent chemotherapeutic agent doxorubicin (DOX).…”

Section: Resultsmentioning

confidence: 99%

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Luo,

Sun,

Tan

et al. 2023

Pharmaceutics

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Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

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Section: Resultsmentioning

confidence: 99%

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Luo,

Sun,

Tan

et al. 2023

Pharmaceutics

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“…IL-11Rα is activated by its ligand IL-11, which can activate multiple signaling cascades in its target cells and is considered an important regulator of bone homeostasis. IL-11 and IL-11R are both expressed in OS in situ and in lung metastases, and are markers of high-risk OS, while the expression of IL-11Rα is absent in neighboring health lung tissue ( 77 , 78 ). IL-11Rα-CAR-T cells are able to effectively eliminate OS cells in vitro , and have been observed to specifically target and accumulate in OS lung metastases following intravenous administration, while demonstrating no accumulation in the surrounding health lung tissue.…”

Section: Antigen Targetsmentioning

confidence: 99%

Chimeric antigen receptor T cells in the treatment of osteosarcoma (Review)

Yu,

Jiang,

Wang

et al. 2024

Int J Oncol

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Osteosarcoma (OS) is a frequently occurring primary bone tumor, mostly affecting children, adolescents and young adults. Before 1970, surgical resection was the main treatment method for OS, but the clinical results were not promising. Subsequently, the advent of chemotherapy has improved the prognosis of patients with OS. However, there is still a high incidence of metastasis or recurrence, and chemotherapy has several side effects, thus making the 5-year survival rate markedly low. Recently, chimeric antigen receptor T (CAR-T) cell therapy represents an alternative immunotherapy approach with significant potential for hematologic malignancies. Nevertheless, the application of CAR-T cells in the treatment of OS faces numerous challenges. The present review focused on the advances in the development of CAR-T cells to improve their clinical efficacy, and discussed ways to overcome the difficulties faced by CAR T-cell therapy for OS.

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“…This system involved functionalizing REDOX-sensitive polymersomes with IL-11 ligand and encapsulating the chemotherapy drug Dox. Their findings showed that IL11-PDox enhanced the efficacy of chemotherapy in mouse models of recurrent and metastatic osteosarcoma, suggesting a potential combination strategy of IL-11Ra-targeted therapy with chemotherapy for advanced osteosarcoma (94). Although no toxic reactions were observed in CAR-T trials targeting IL-11Ra, concerns have been raised about the efficiency of IL-11Ra-targeted therapy because of its underexpression in osteosarcoma (93).…”

Section: Interleukin-11 Receptor Alphamentioning

confidence: 99%

“…PD-L1 inhibitors are believed to reverse the rapid depletion of CAR-T cells (25, 116). Chemotherapeutic agents can enhance CAR-T cell trafficking, infiltration, and anti-tumor efficacy in solid tumors; however, the dosage and side effects of these agents must be carefully considered (71,94,117). Zheng et al suggested that PI3K inhibitors could maintain the hypofunctional state of CAR-T cells without affecting T cell expansion, thereby improving their persistence and reducing tumor burden (118).…”

Section: Therapeutic Durability Of Car-t Cellsmentioning

confidence: 99%

Current status and future challenges of CAR-T cell therapy for osteosarcoma

Li,

Zhang,

Shang

2023

Front. Immunol.

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Osteosarcoma, the most common bone malignancy in children and adolescents, poses considerable challenges in terms of prognosis, especially for patients with metastatic or recurrent disease. While surgical intervention and adjuvant chemotherapy have improved survival rates, limitations such as impractical tumor removal or chemotherapy resistance hinder the treatment outcomes. Chimeric antigen receptor (CAR)-T cell therapy, an innovative immunotherapy approach that involves targeting tumor antigens and releasing immune factors, has shown significant advancements in the treatment of hematological malignancies. However, its application in solid tumors, including osteosarcoma, is constrained by factors such as low antigen specificity, limited persistence, and the complex tumor microenvironment. Research on osteosarcoma is ongoing, and some targets have shown promising results in pre-clinical studies. This review summarizes the current status of research on CAR-T cell therapy for osteosarcoma by compiling recent literature. It also proposes future research directions to enhance the treatment of osteosarcoma.

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IL-11Rα-targeted nanostrategy empowers chemotherapy of relapsed and patient-derived osteosarcoma

Cited by 7 publications

References 39 publications

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Chimeric antigen receptor T cells in the treatment of osteosarcoma (Review)

Current status and future challenges of CAR-T cell therapy for osteosarcoma

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