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A Universal Therapeutic Vaccine Leveraging Autologous Pre-Existing Immunity to Eliminate in Situ Uniformly Engineered Heterogeneous Tumor Cells.

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January 2025

Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, P. R. China.

Tumor vaccines that activate the autologous immune system to eliminate tumor cells represent a promising approach in cancer immunotherapy. However, challenges such as tumor heterogeneity, limited antigen selection, insufficient antigen presentation, and the slow onset of de novo immune responses have resulted in poor universality and suboptimal response rates. In contrast, pathogen-specific pre-existing immunity acquired through infection or vaccination, can rapidly generate a more potent and enduring immune response upon re-encounter with the same antigen.

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We investigated a novel cancer immunotherapy strategy that effectively suppresses tumor growth in multiple solid tumor models and significantly extends the lifespan of tumor-bearing mice by introducing pathogen antigens into tumors via mRNA-lipid nanoparticles. The pre-existing immunity against the pathogen antigen can significantly enhance the efficacy of this approach. In mice previously immunized with BNT162b2, an mRNA-based COVID-19 vaccine encoding the spike protein of the SARS-CoV-2 virus, intratumoral injections of the same vaccine efficiently tagged the tumor cells with mRNA-expressed spike protein.

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Vaccination represents a core preventive strategy for public health, with interrelated and multifaceted effects across health and socioeconomic domains. Beyond immediate disease prevention, immunization positively influences downstream health outcomes by mitigating complications of preexisting comorbidities and promoting healthy aging. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, and respiratory syncytial virus (RSV) are common respiratory viruses responsible for broad societal cost and substantial morbidity and mortality, particularly among at-risk individuals, including older adults and people with frailty or certain comorbid conditions.

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AAV vectors show promise for gene therapy; however, kidney gene transfer remains challenging. Here we conduct a barcode-seq-based comparison of 47 AAV capsids administered through different routes in mice, followed by individual validation. We find that local delivery of AAV-KP1, but not AAV9, via the renal vein or pelvis effectively transduces proximal tubules with minimal off-target liver transduction, while systemic AAV9, but not AAV-KP1, enhances proximal tubule and podocyte transduction in chronic kidney disease.

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Mathematical comparison of protocols for adapting a bacteriophage to a new host.

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Institute for Modeling Collaboration and Innovation, University of Idaho, 875 Perimeter drive, Moscow, ID 83844, United States.

Interest in phage therapy-the use of bacterial viruses to treat infections-has increased recently because of the rise of infections with antibiotic-resistant bacteria and the failure to develop new antibiotics to treat those infections. Phages have shown therapeutic promise in recent work, and successful treatment minimally requires giving the patient a phage that will grow on their infecting bacterium. Although nature offers a bountiful and diverse supply of phages, there have been a surprising number of patient infections that could not be treated with phages because no suitable phage was found to kill the patient's bacterium.

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