为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Enhancement of dendritic cell immunotherapy by recalling antigens for hepatocellular carcinoma in mice.
Enhancement of dendritic cell immunotherapy by recalling antigens for hepatocellular carcinoma in mice.
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树突状细胞(DC)免疫疗法对小鼠大型肝癌的治疗效果并不理想。
采用基于DC的免疫疗法治疗直径为6 ± 1 mm的Hepa1-6肿瘤,并通过加强肿瘤抗原来增强疗效。
基于DC的疫苗接种后,CD4 + 和CD8 + T细胞发生收缩并转化为记忆表型细胞。当T细胞被重新刺激时,从通过肿瘤抗原注射加强的小鼠中获得的T细胞显示出最高的增殖能力。当治疗患有大型肿瘤的小鼠时,通过肿瘤抗原加强的基于DC的疫苗接种和额外输注DC分别产生了50%和23.1%的治愈率。
DC疫苗接种诱导了效应记忆细胞。通过DC或肿瘤抗原重新激活的抗原提呈提高了患有大型肿瘤小鼠的治愈率。肝细胞癌是最常见的肝脏恶性肿瘤,且常在晚期被发现。免疫检查点抑制剂联合分子靶向药物是治疗晚期肝细胞癌的新策略,可获得30%的客观缓解率。然而,对于对免疫检查点抑制剂联合分子靶向药物无反应的患者,我们仍需要另一种治疗方法。基于树突状细胞的免疫疗法是晚期肝细胞癌的治疗方法之一。在这项动物研究中,树突状细胞可以激活T淋巴细胞以杀死癌细胞。树突状细胞还可以诱导记忆T淋巴细胞,这些细胞可以通过加强肿瘤抗原来产生反应并提高治疗效果。这种治疗策略,即输注树突状细胞后注射肿瘤抗原,未来可以转化为临床实践。
Background: The therapeutic efficacy of dendritic cell (DC)-immunotherapy for large hepatoma in mice is unsatisfactory. Materials & methods: DC-based immunotherapy was used to treat Hepa1-6 tumors measuring 6 ± 1 mm in diameter, enhanced by boosting tumor antigens. Results: CD4 + and CD8 + T-cells were contracted and transformed into memory phenotypic cells after DC-based vaccination. When T-cells were re-stimulated, T-cells obtained from mice boosted by tumor antigen injection showed highest proliferation capacity.
When mice with large tumors were treated, DC-based vaccination boosted by tumor antigen and an additional DC-infusion yielded curative rates of 50% and 23. 1%, respectively. Conclusion: DC vaccination induced effector memory cells. Antigen presentation recalled by DC or tumor antigens increased the curative rate in mice with large tumors.
Hepatocellular carcinoma is the most common liver malignancy and is often found at advanced stage. Immune checkpoint inhibitor combined with a molecular targeting agent is a new strategy for the treatment of advanced hepatocellular carcinoma and yields 30% of objective response rate.
However, we still need another treatment for the patients who are not responsive to immune checkpoint inhibitor combined with a molecular targeting agent. Dendritic cell-based immunotherapy is one of the treatments for advanced hepatocellular carcinoma. In this animal study, dendritic cells can activate T-lymphocytes to kill cancer cells.
Dendritic cells can also induce memory T-lymphocytes, which can be reactive by boost tumor antigens and increase therapeutic efficacy. This treatment strategy, dendritic cell infusion followed by tumor-antigen injection, can be translated into clinical practice in the future.
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