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Immunomodulatory nanoparticles activate cytotoxic T cells for enhancement of the effect of cancer immunotherapy
Nanoscale ( IF 5.8 ) Pub Date : 2024-09-06 , DOI: 10.1039/d4nr01780c Kory Wells 1, 2 , Tongrui Liu 1 , Lei Zhu 1 , Lily Yang 1, 2
Nanoscale ( IF 5.8 ) Pub Date : 2024-09-06 , DOI: 10.1039/d4nr01780c Kory Wells 1, 2 , Tongrui Liu 1 , Lei Zhu 1 , Lily Yang 1, 2
Affiliation
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Cancer immunotherapy represents a promising targeted treatment by leveraging the patient's immune system or adoptive transfer of active immune cells to selectively eliminate cancer cells. Despite notable clinical successes, conventional immunotherapies face significant challenges stemming from the poor infiltration of endogenous or adoptively transferred cytotoxic T cells in tumors, immunosuppressive tumor microenvironment and the immune evasion capability of cancer cells, leading to limited efficacy in many types of solid tumors. Overcoming these hurdles is essential to broaden the applicability of immunotherapies. Recent advances in nanotherapeutics have emerged as an innovative tool to overcome these challenges and enhance the therapeutic potential of tumor immunotherapy. The unique biochemical and biophysical properties of nanomaterials offer advantages in activation of immune cells in vitro for cell therapy, targeted delivery, and controlled release of immunomodulatory agents in vivo. Nanoparticles are excellent carriers for tumor associated antigens or neoantigen peptides for tumor vaccine, empowering activation of tumor specific T cell responses. By precisely delivering immunomodulatory agents to the tumor site, immunoactivating nanoparticles can promote tumor infiltration of endogenous T cells or adoptively transferred T cells into tumors, to overcoming delivery and biological barriers in the tumor microenvironment, augmenting the immune system's ability to recognize and eliminate cancer cells. This review provides an overview of the current advances in immunotherapeutic approaches utilizing nanotechnology. With a focus on discussions concerning strategies to enhance activity and efficacy of cytotoxic T cells and explore the intersection of engineering nanoparticles and immunomodulation aimed at bolstering T cell-mediated immune responses, we introduce various nanoparticle formulations designed to deliver therapeutic payloads, tumor antigens and immunomodulatory agents for T cell activation. Diverse mechanisms through which nanoparticle-based approaches influence T cell responses by improving antigen presentation, promoting immune cell trafficking, and reprogramming immunosuppressive tumor microenvironments to potentiate anti-tumor immunity are examined. Additionally, the synergistic potential of combining nanotherapeutics with existing immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapies is explored. In conclusion, this review highlights emerging research advances on activation of cytotoxic T cells using nanoparticle agents to support the promises and potential applications of nanoparticle-based immunomodulatory agents for cancer immunotherapy.
中文翻译：
免疫调节纳米颗粒激活细胞毒性 T 细胞以增强癌症免疫治疗的效果
癌症免疫疗法是一种很有前途的靶向治疗，它利用患者的免疫系统或活性免疫细胞的过继转移来选择性地消除癌细胞。尽管取得了显著的临床成功，但传统免疫疗法面临着重大挑战，因为肿瘤中内源性或过继转移的细胞毒性 T 细胞浸润不良、免疫抑制性肿瘤微环境和癌细胞的免疫逃避能力，导致在许多类型的实体瘤中疗效有限。克服这些障碍对于扩大免疫疗法的适用性至关重要。纳米治疗学的最新进展已成为克服这些挑战并增强肿瘤免疫治疗潜力的创新工具。纳米材料独特的生化和生物物理特性在体外激活免疫细胞以进行细胞治疗、靶向递送和体内免疫调节剂的控释方面具有优势。纳米颗粒是肿瘤相关抗原或肿瘤疫苗新抗原肽的优秀载体，可激活肿瘤特异性 T 细胞反应。免疫激活纳米颗粒通过将免疫调节剂精确递送至肿瘤部位，可促进肿瘤浸润内源性 T 细胞或过继转移 T 细胞进入肿瘤，以克服肿瘤微环境中的递送和生物障碍，增强免疫系统识别和消除癌细胞的能力。本综述概述了利用纳米技术的免疫治疗方法的当前进展。 我们重点介绍了有关增强细胞毒性 T 细胞活性和功效的策略的讨论，并探索旨在增强 T 细胞介导的免疫反应的工程纳米颗粒和免疫调节的交叉点，我们介绍了各种纳米颗粒制剂，旨在提供治疗有效载荷、肿瘤抗原和免疫调节剂用于 T 细胞活化。研究了基于纳米颗粒的方法通过改善抗原呈报、促进免疫细胞运输和重编程免疫抑制肿瘤微环境以增强抗肿瘤免疫力来影响 T 细胞反应的不同机制。此外，还探索了纳米疗法与现有免疫疗法（如免疫检查点抑制剂和过继性 T 细胞疗法）相结合的协同潜力。总之，本综述重点介绍了使用纳米颗粒剂激活细胞毒性 T 细胞的新兴研究进展，以支持基于纳米颗粒的免疫调节剂在癌症免疫治疗中的前景和潜在应用。
更新日期：2024-09-11
中文翻译：
免疫调节纳米颗粒激活细胞毒性 T 细胞以增强癌症免疫治疗的效果
癌症免疫疗法是一种很有前途的靶向治疗，它利用患者的免疫系统或活性免疫细胞的过继转移来选择性地消除癌细胞。尽管取得了显著的临床成功，但传统免疫疗法面临着重大挑战，因为肿瘤中内源性或过继转移的细胞毒性 T 细胞浸润不良、免疫抑制性肿瘤微环境和癌细胞的免疫逃避能力，导致在许多类型的实体瘤中疗效有限。克服这些障碍对于扩大免疫疗法的适用性至关重要。纳米治疗学的最新进展已成为克服这些挑战并增强肿瘤免疫治疗潜力的创新工具。纳米材料独特的生化和生物物理特性在体外激活免疫细胞以进行细胞治疗、靶向递送和体内免疫调节剂的控释方面具有优势。纳米颗粒是肿瘤相关抗原或肿瘤疫苗新抗原肽的优秀载体，可激活肿瘤特异性 T 细胞反应。免疫激活纳米颗粒通过将免疫调节剂精确递送至肿瘤部位，可促进肿瘤浸润内源性 T 细胞或过继转移 T 细胞进入肿瘤，以克服肿瘤微环境中的递送和生物障碍，增强免疫系统识别和消除癌细胞的能力。本综述概述了利用纳米技术的免疫治疗方法的当前进展。 我们重点介绍了有关增强细胞毒性 T 细胞活性和功效的策略的讨论，并探索旨在增强 T 细胞介导的免疫反应的工程纳米颗粒和免疫调节的交叉点，我们介绍了各种纳米颗粒制剂，旨在提供治疗有效载荷、肿瘤抗原和免疫调节剂用于 T 细胞活化。研究了基于纳米颗粒的方法通过改善抗原呈报、促进免疫细胞运输和重编程免疫抑制肿瘤微环境以增强抗肿瘤免疫力来影响 T 细胞反应的不同机制。此外，还探索了纳米疗法与现有免疫疗法（如免疫检查点抑制剂和过继性 T 细胞疗法）相结合的协同潜力。总之，本综述重点介绍了使用纳米颗粒剂激活细胞毒性 T 细胞的新兴研究进展，以支持基于纳米颗粒的免疫调节剂在癌症免疫治疗中的前景和潜在应用。
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