CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Hydrogel-based delivery of cytokines in cancer immunotherapy: Latest evidence and therapeutic outcomes.
Hydrogel-based delivery of cytokines in cancer immunotherapy: Latest evidence and therapeutic outcomes.
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细胞因子是强效免疫调节剂,在癌症免疫治疗中前景广阔,但全身给药受快速降解、脱靶毒性和肿瘤浸润不足限制。水凝胶递送系统提供了一种新方法:将细胞因子包封在生物相容性、可降解聚合物中,从而在肿瘤微环境(TME)内实现局部、持续释放。注射型和刺激响应型等可定制水凝胶平台可保护细胞因子免受蛋白水解降解,提高生物利用度并减轻全身有害作用。
此外,水凝胶可响应pH变化或酶活性等TME特异信号,实现精准可控释放,从而增强免疫应答。临床前研究提示,这些方法可增强抗肿瘤免疫、抑制肿瘤增殖,并通过与免疫检查点抑制剂(ICI)及包括CAR-T 细胞疗法在内的细胞疗法协同作用防止复发。尽管进展令人鼓舞,规模化生产、重现性和监管审批等问题仍待解决,临床应用前需进一步优化。本综述讨论水凝胶介导细胞因子递送的独特潜力,重点介绍其生物相容性、释放机制及融入联合治疗方案的能力。作者将这些水凝胶描述为有望改变癌症免疫治疗的“凝胶战士”,可用更精准、更安全、更有效的方式激活免疫系统抗击肿瘤。
Cytokines serve as potent immunomodulators with considerable promise in cancer immunotherapy.
However, their systemic administration is limited by rapid breakdown, off-target toxicity, and inadequate tumor infiltration. Hydrogel-based delivery systems offer a novel approach by encapsulating cytokines in biocompatible, biodegradable polymers, thereby facilitating localized, sustained release within the tumor microenvironment (TME). These customizable platforms, such as injectable and stimulus-responsive hydrogels, safeguard cytokines against proteolytic degradation, improve bioavailability, and mitigate systemic deleterious effects.
Moreover, hydrogels can provide accurate, controlled release by responding to TME-specific cues, such as pH variations or enzyme activity, thus enhancing the immune response. Preclinical research suggests that these methods can enhance anti-tumor immune responses, inhibit tumor proliferation, and prevent recurrence through synergistic interactions with immune checkpoint inhibitors (ICIs) and cell-based therapies, including chimeric antigen receptor (CAR) T-cell therapy.
Notwithstanding these encouraging advancements, concerns such as scalability, reproducibility, and regulatory approval persist, necessitating further refinement for clinical employment. This review discusses the distinct potential of hydrogel-mediated cytokine administration, emphasizing its biocompatibility, release mechanisms, and capacity to integrate into combination therapy regimens.
We introduce these hydrogels as "gel-based warriors" ready to transform cancer immunotherapy by providing a focused, safer, and more effective approach to activating the immune system against tumors.
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