Fu Wenxin, Li Qianqian, Sheng Jingyi, Wu Haoan, Ma Ming, Zhang Yu
State Key Laboratory of Digital Medical Engineering, Basic Medicine Research and Innovation Center of Ministry of Education, Southeast University, Nanjing 211102, China.
Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Gels. 2024 Dec 19;10(12):838. doi: 10.3390/gels10120838.
Tumor whole-cell vaccines are designed to introduce a wide range of tumor-associated antigens into the body to counteract the immunosuppression caused by tumors. In cases of lymphoma of which the specific antigen is not yet determined, the tumor whole-cell vaccine offers distinct advantages. However, there is still a lack of research on an effective preparation method for the lymphoma whole-cell vaccine. To solve this challenge, we prepared a whole-cell vaccine derived from non-Hodgkin B-cell lymphoma (A20) via the photothermal effect mediated by Prussian blue nanoparticles (PBNPs). The immune activation effect of this vaccine against lymphoma was verified at the cellular level. The PBNPs-treated A20 cells underwent immunogenic cell death (ICD), causing the loss of their ability to form tumors while retaining their ability to trigger an immune response. A20 cells that experienced ICD were further ultrasonically crushed to prepare the A20 whole-cell vaccine with exposed antigens and enhanced immunogenicity. The A20 whole-cell vaccine was able to activate the dendritic cells (DCs) to present antigens to T cells and trigger specific immune responses against lymphoma. Whole-cell vaccines are primarily administered through direct injection, a method that often results in low delivery efficiency and poor patient compliance. Comparatively, the microneedle patch system provides intradermal delivery, offering enhanced lymphatic absorption and improved patient adherence due to its minimally invasive approach. Thus, we developed a porous microneedle patch system for whole-cell vaccine delivery using Gelatin Methacryloyl (GelMA) hydrogel and n-arm-poly(lactic-co-glycolic acid) (n-arm-PLGA). This whole-cell vaccine combined with porous gel microneedle patch delivery system has the potential to become a simple immunotherapy method with controllable production and represents a promising new direction for the treatment of lymphoma.
肿瘤全细胞疫苗旨在将多种肿瘤相关抗原引入体内，以对抗肿瘤引起的免疫抑制。在特定抗原尚未确定的淋巴瘤病例中，肿瘤全细胞疫苗具有明显优势。然而，对于淋巴瘤全细胞疫苗的有效制备方法仍缺乏研究。为应对这一挑战，我们通过普鲁士蓝纳米颗粒（PBNPs）介导的光热效应，制备了一种源自非霍奇金B细胞淋巴瘤（A20）的全细胞疫苗。该疫苗对淋巴瘤的免疫激活作用在细胞水平得到了验证。经PBNPs处理的A20细胞发生免疫原性细胞死亡（ICD），导致其失去形成肿瘤的能力，同时保留触发免疫反应的能力。经历ICD的A20细胞进一步超声破碎，以制备具有暴露抗原和增强免疫原性的A20全细胞疫苗。A20全细胞疫苗能够激活树突状细胞（DCs）将抗原呈递给T细胞，并触发针对淋巴瘤的特异性免疫反应。全细胞疫苗主要通过直接注射给药，这种方法往往导致递送效率低和患者依从性差。相比之下，微针贴片系统提供皮内递送，由于其微创方法，具有增强的淋巴吸收和改善的患者依从性。因此，我们使用甲基丙烯酰化明胶（GelMA）水凝胶和n臂聚（乳酸-共-乙醇酸）（n臂-PLGA）开发了一种用于全细胞疫苗递送的多孔微针贴片系统。这种全细胞疫苗与多孔凝胶微针贴片递送系统相结合，有可能成为一种生产可控的简单免疫治疗方法，代表了淋巴瘤治疗的一个有前途的新方向。
