Recently, a significant scientific breakthrough was achieved through the collaboration between Professor Kuirong Jiang's team at the Pancreas Center of the First Affiliated Hospital and Professor Xiao Zhao's team at the National Center for Nanoscience and Technology. Together, they developed a novel personalized cancer vaccine based on bacterial-derived nanovesicles that enhance antigen presentation signals, offering new insights into cancer immunotherapy. The research findings were published in the prestigious international journal Advanced Materials (impact factor: 27.4) under the title An OMV-Based Nanovaccine as Antigen Presentation Signal Enhancer for Cancer Immunotherapy.
Cancer vaccines represent a crucial area of research in cancer immunotherapy. These vaccines stimulate the immune system to recognize and process tumor antigens, thereby triggering an immune response specifically targeting antigen-expressing cells. This mechanism ultimately leads to the elimination of tumor cells and helps prevent cancer recurrence. However, tumor burden can disrupt the second signaling between antigen-presenting cells and T cells, affecting both co-stimulatory and co-inhibitory signals. Such disruptions hinder the antigen presentation process, ultimately leading to the failure of cancer vaccines. Therefore, a major challenge in cancer vaccine development is to enhance co-stimulatory signals while reducing co-inhibitory signals, ensuring the proper coordination of second signaling and achieving effective antigen presentation.
To address this challenge, the research team develops a novel cancer vaccine utilizing bacterial-derived nanovesicles to enhance antigen presentation signals. First, leveraging a molecular glue system, this vaccine enables a “plug-and-play” approach for the rapid display of tumor antigens, providing a flexible platform for personalized cancer treatment. Additionally, it incorporates an antibody-anchoring protein on the surface, allowing the introduction of PD-L1 antibodies (αPD-L1) to regulate the second signaling. During antigen presentation, this vaccine effectively blocks the PD-L1/PD-1 interaction while enhancing both the binding strength and abundance of CD80 on antigen-presenting cells with CD28 on T cells. By simultaneously upregulating the first signal and modulating the second signal (reducing co-inhibitory signals while increasing co-stimulatory signals), the vaccine significantly improves antigen presentation and T-cell activation. Both in vitro and in vivo studies have demonstrated its potent antitumor effects.
This study highlights that PD-L1 antibodies not only inhibit immune evasion of tumor cells during the immune killing phase but also synergize with cancer vaccines in the immune priming phase, enhancing the activation of T cells by antigen-presenting cells. This discovery provides new insights into immune checkpoint blockade therapy, expands its potential applications, and offers renewed hope for immunotherapy in patients with pancreatic cancer and other challenging malignancies.
Professor Kuirong Jiang and Dr. Yazhou Wang from the Pancreas Center of the First Affiliated Hospital with Nanjing Medical University, along with Professor Xiao Zhao from the National Center for Nanoscience and Technology, are co-corresponding authors. PhD student Yichao Lu from the Pancreas Center and Dr. Nana Ma from the National Center for Nanoscience and Technology are co-first authors.
Link to the paper:
https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202413392
(Drafted by the Pancreas Center of the First Affiliated Hospital; Reviewed by Jiang Kuirong; Translation by Wang Yazhou; Translation Revised by Zhang Bei)
