Department of Radiology, Molecular Imaging Program at Stanford, Canary Center for Cancer Early Detection, Stanford University, Palo Alto, CA, USA.
Molecular Imaging Program at Stanford (MIPS), Canary Center for Cancer Early Detection at Stanford, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94304, USA.
J Exp Clin Cancer Res. 2022 Oct 12;41(1):299. doi: 10.1186/s13046-022-02501-3.
Therapeutic strategies engaging the immune system against malignant cells have revolutionized the field of oncology. Proficiency of dendritic cells (DCs) for antigen presentation and immune response has spurred interest on DC-based vaccines for anti-cancer therapy. However, despite favorable safety profiles in patients, current DC-vaccines have not yet presented significant outcome due to technical barriers in active DC delivery, tumor progression, and immune dysfunction. To maximize the therapeutic response, we present here a unique cell-free DC-based vaccine capable of lymphoid organ targeting and eliciting T-cell-mediated anti-tumor effect.
We developed this novel immunotheranostic platform using plasma membranes derived from activated DCs incorporated into ultrasound contrast microbubbles (MBs), thereby offering real-time visualization of MBs' trafficking and homing in vivo. Human PBMC-derived DCs were cultured ex vivo for controlled maturation and activation using cell membrane antigens from breast cancer cells. Following DC membrane isolation, immunotheranostic microbubbles, called DC-iMBs, were formed for triple negative breast cancer treatment in a mouse model harboring a human reconstituted immune system.
Our results demonstrated that DC-iMBs can accumulate in lymphoid organs and induce anti-tumor immune response, which significantly reduced tumor growth via apoptosis while increasing survival length of the treated animals. The phenotypic changes in immune cell populations upon DC-iMBs delivery further confirmed the T-cell-mediated anti-tumor effect.
These early findings strongly support the potential of DC-iMBs as a novel immunotherapeutic cell-free vaccine for anti-cancer therapy.
利用免疫系统对抗恶性细胞的治疗策略彻底改变了肿瘤学领域。树突状细胞（DC）在抗原呈递和免疫反应方面的优势激发了人们对基于 DC 的癌症治疗疫苗的兴趣。然而，尽管在患者中具有良好的安全性，当前的 DC 疫苗由于主动 DC 递呈、肿瘤进展和免疫功能障碍方面的技术障碍，尚未取得显著效果。为了最大限度地提高治疗反应，我们提出了一种独特的无细胞基于 DC 的疫苗，能够靶向淋巴器官并引发 T 细胞介导的抗肿瘤作用。
我们使用源自激活的 DC 的质膜开发了这种新型免疫治疗诊断平台，从而能够实时可视化 MBs 的体内迁移和归巢。用人外周血单核细胞来源的 DC 在体外进行培养，通过乳腺癌细胞的细胞膜抗原进行受控成熟和激活。在 DC 膜分离后，形成免疫治疗诊断微泡，称为 DC-iMBs，用于在携带人重建免疫系统的小鼠模型中治疗三阴性乳腺癌。
我们的结果表明，DC-iMBs 可以在淋巴器官中积累并诱导抗肿瘤免疫反应，通过凋亡显著减少肿瘤生长，同时延长治疗动物的生存时间。在 DC-iMBs 给药后免疫细胞群体的表型变化进一步证实了 T 细胞介导的抗肿瘤作用。
这些早期发现强烈支持 DC-iMBs 作为一种新型无细胞免疫治疗癌症治疗的潜在应用。
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