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肿瘤靶向肽 TMTP1 修饰的抗原捕获纳米疫苗联合化疗和 PD-L1 阻断可有效抑制卵巢癌的生长。

Tumor targeting peptide TMTP1 modified Antigen capture Nano-vaccine combined with chemotherapy and PD-L1 blockade effectively inhibits growth of ovarian cancer.

机构信息

Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Nanobiotechnology. 2024 Aug 13;22(1):483. doi: 10.1186/s12951-024-02744-6.

DOI:10.1186/s12951-024-02744-6
PMID:39138475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11320875/
Abstract

The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body's immune potential, providing an eutherapeutic strategy for the treatment of OC.

摘要

卵巢癌 (OC) 的死亡率长期以来一直是妇科恶性肿瘤中最高的。尽管 OC 被认为是一种免疫原性肿瘤,但免疫疗法的效果并不理想。免疫抑制微环境是原因之一,而缺乏被认可的有效疫苗抗原是另一个原因。化疗是 OC 最常用的治疗方法之一,在治疗过程中会产生化疗相关抗原 (CAA),并表现出原位疫苗的效果。在此,我们设计了一种抗原捕获纳米疫苗 NP-TP1@M-M,该疫苗表面组装了肿瘤靶向肽 TMTP1 和树突状细胞 (DC) 受体甘露糖,核心包裹了佐剂单磷酰脂质 A (MPLA),并封装在聚 (D,L-丙交酯-共-乙交酯) (PLGA) 纳米颗粒中。PLGA 本身具有抗原捕获能力。TMTP1 是我们的研究团队筛选出的一种肿瘤归巢肽,具有广泛而优异的肿瘤靶向能力。经过这些修饰,NP-TP1@M-M 在化疗后可以捕获和富集更多的肿瘤特异性抗原,刺激 DC 成熟,激活适应性免疫,并与免疫检查点阻断相结合,最大限度地释放机体的免疫潜能,为 OC 的治疗提供了一种辅助治疗策略。

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