Researchers use nanotechnology to destroy and prevent relapse of solid tumor cancers

Onderzoekers gebruiken nanotechnologie om terugval van solide tumorkankers te vernietigen en te voorkomen

Generation and characterization of DCNV-rAd-Ag. a, Generation of DCNVs derived from adenovirus-infected mature dendritic cells. (1) The tumor-specific antigen genes were genetically engineered into the adenovirus vector. (2) Recombinant adenovirus infected the immature DC2.4 cells to express and stimulate the modified antigen on the cell surface. (3) Differentiation, maturation and antigen presentation. (4) Harvesting the induced mature cell membrane and preparation of DCNV-rAd-Ag. b, Schematic illustration of DCNV-rAd-Ag generation. c, d, Cryoelectron microscopy (c) and dynamic light scattering analyzes (d) showed uniform DCNV-rAd-Ag (approximately 108 nm mean diameter, polydispersity index = 0.14) with a vesicle-like morphology. Scale bar, 50 nm. e, The western blot on DCNV-rAd-GFP membrane proteins shows a similar surface protein content compared to that of the parental cells. Panels ce show representative results from two independent experiments with comparable results. f, Comparison of upregulated immune response related proteins in NVs and DCs. g, The relative abundance of antigen presentation and migration-related proteins on DCNV-rAd-GFP. rpm, revolutions per minute. CCR, CC chemokine receptor; CXCR, CXC chemokine receptor; EpCAM, epithelial cellular adhesion molecule; ICAM 1, intercellular adhesion molecule 1; pMHC-I, peptide-large histocompatibility complex class I. Credit: Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01098-0

As people around the world look forward to longer life expectancy, malignant cancers continue to pose a threat to human health. The exploration and development of immunotherapy is aimed at finding new breakthroughs for the treatment of solid tumors.

The successful establishment of antitumor immunity requires the activation, expansion and differentiation of antigen-specific lymphocytes. This process largely depends on specific interactions between different T cells and antigen-presenting cells (APCs) in the body. However, existing tumor vaccines, such as neoantigen vaccines and various vector vaccines, all rely on random interactions with APCs in the body. In addition, inappropriate interactions can lead to the silencing of other immune responses.

Although immunotherapy based on immune checkpoints has been shown to have great potential, only a small proportion of patients fully respond to this therapy and the relevant molecular mechanisms need further investigation. However, this delivery method is complex and inefficient.

In a groundbreaking development, a team of scientists led by Narat Muzayyin Chairman Professor Chen Xiaoyuan of NUS Yong Loo Lin School of Medicine and Professor Liu Gang of Xiamen University has formulated a new vaccine that showed high efficacy in treating solid tumors. complete clearance of solid tumors and inducing prolonged immune memory. This prevents a relapse of the tumor growth that the patient originally had and provides immunity against similar tumor types. This was proven by applying this vaccine to melanoma tumor models. Their results have been published in Nature Nanotechnology

The team was able to develop a dendritic cell membrane (a type of APC) that was used to naturally boost the immune system and activate multidimensional anti-tumor immunity. This was done through an antigen self-presentation and immunosuppression reverse nanovesicle vaccine platform, leading the team to use its nickname ASPIRE.

The ASPIRE vaccine system can rapidly elicit appropriate, antigen-specific immune responses in a way that traditional vaccine methods could not. This mode of antigen presentation significantly improves the efficiency of immune activation, allowing for the high efficacy of this new vaccine compared to other currently available vaccines. In addition, the vaccine can activate both previously unexposed T cells and depleted T cells, promoting ASPIRE’s superior anti-tumor immune capabilities.

“We are excited about the potential of this platform technology for further application in other diseases, such as chronic viral infection, where T cell depletion often occurs during infection and prevents optimal viral control,” said Prof. Chen. “Then the team hopes to establish a standard operating procedure for scaled synthesis of the vaccine, with good quality control of the membrane vesicles, for clinical translation,” he added.

Professor Chng Wee Joo, senior advisor to the Department of Hematology of the Department of Hematology-Oncology at the National University Cancer Institute, Singapore and myeloma specialist, spoke independently about the study, saying: “The field of cancer immunotherapy offers tremendous hope for cancer patients. however, some shortcomings with current technologies.The current innovation of Prof Chen and his colleagues has overcome some of these shortcomings and the effectiveness and
durability of the immune response to these treatments. This will bring significant progress that will have a significant impact on patients.”

Emerging vaccine nanotechnology

More information:
Chao Liu et al, A nanovaccine for antigen self-presentation and reversal of immunosuppression as a personalized cancer immunotherapy strategy, Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01098-0

Provided by the National University of Singapore

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