Zhao Zhongchao, Ledezma Debbie K, Affonso de Oliveira Jessica Fernanda, Omole Anthony O, Steinmetz Nicole F
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
Center for Nano-ImmunoEngineering, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Nat Commun. 2025 May 30;16(1):5047. doi: 10.1038/s41467-025-60239-w.
Current treatment options for ovarian cancer are limited to surgery to remove tumor tissues and chemotherapy. Although such treatments could provide a short period of remission, most patients still experience recurrent metastatic diseases. Here we present a nanotechnology-based personalized cancer vaccine that can be administrated to patients during the remission stage to prevent recurrent diseases. Autologous tumor cell lysates (TCL) are intriguing, personalized antigens that could be extracted from surgically recovered tumor tissues from patients containing all neoantigens. As proof of concept, we use TCL isolated from a murine ovarian cancer cell line. TCL are first encapsulated in liposomes (TCL-Lip), which are then attached to cowpea mosaic virus (CPMV), a plant virus as a potent adjuvant. Using the ID8-Defb29/Vegf-a-Luc tumor model in female mice, the TCL-Lip-CPMV conjugate vaccine protects mice from tumor challenge by improving antigen processing and presentation, priming an adaptive anti-tumor immunity. Using ovalbumin (OVA) as a model antigen, OVA-Lip-CPMV vaccination protects mice from lung metastasis post-surgical removal of the primary B16F10-OVA dermal tumors. This research establishes a platform by combining two nanoparticle technologies into a single formulation for the simultaneous delivery of antigens and adjuvants, advancing the development of cancer vaccines and immunotherapies.
目前卵巢癌的治疗选择仅限于手术切除肿瘤组织和化疗。尽管这些治疗方法能提供短期缓解,但大多数患者仍会出现复发性转移性疾病。在此,我们展示了一种基于纳米技术的个性化癌症疫苗,可在缓解期给予患者以预防疾病复发。自体肿瘤细胞裂解物(TCL)是一种引人关注的个性化抗原,可从手术切除的患者肿瘤组织中提取,其中包含所有新抗原。作为概念验证,我们使用从小鼠卵巢癌细胞系中分离出的TCL。TCL首先被包裹在脂质体中(TCL-Lip),然后与豇豆花叶病毒(CPMV)相连,CPMV是一种植物病毒,作为一种有效的佐剂。在雌性小鼠中使用ID8-Defb29/Vegf-a-Luc肿瘤模型,TCL-Lip-CPMV偶联疫苗通过改善抗原加工和呈递,引发适应性抗肿瘤免疫,保护小鼠免受肿瘤攻击。以卵清蛋白(OVA)作为模型抗原,OVA-Lip-CPMV疫苗接种可保护小鼠在手术切除原发性B16F10-OVA皮肤肿瘤后免受肺转移。这项研究通过将两种纳米颗粒技术结合到单一制剂中,用于同时递送抗原和佐剂,建立了一个平台,推动了癌症疫苗和免疫疗法的发展。