The development of personalized anticancer vaccines based on neoantigens represents a new direction in cancer immunotherapy. The latest advancement in dendritic cell (DC) tumor vaccine construction involves loading DC with mRNA-encoding neoantigens, which allows for rapid production and is suitable for personalized preparation. Cell-penetrating peptides (CPPs) are emerging as biological delivery systems in which negatively charged nucleic acids can be wound onto the cationic CPP backbone to form nanoscale complexes. This preparation method facilitates standardization. If DC can express and present neoantigen mRNA at high levels, it holds promising application potential. In this study, we developed a neoantigen-mRNA/DC vaccine using candidate neoantigens from mouse colon cancer (MC38) and examined its immune and antitumor effects. The results demonstrated that neoantigen-mRNA/DC vaccines induced strong T cell immune responses and exhibited significant antitumor effects, effectively preventing tumor growth. Our study provides an experimental basis for further optimizing the preparation of DC vaccines and reducing their costs.
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http://dx.doi.org/10.1038/s41435-024-00305-3 | DOI Listing |
NPJ Precis Oncol
January 2025
Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
KRAS-specific inhibitors have shown promising antitumor effects, especially in non-small cell lung cancer, but limited efficacy in colorectal cancer (CRC) patients. Recent studies have shown that EGFR-mediated adaptive feedback mediates primary resistance to KRAS inhibitors, but the other resistance mechanisms have not been identified. In this study, we investigated intrinsic resistance mechanisms to KRAS inhibitors using patient-derived CRC cells (CRC-PDCs).
View Article and Find Full Text PDFNat Med
January 2025
Department of Medicine-Medical Oncology, University of Colorado Cancer Center, Denver, CO, USA.
Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.
View Article and Find Full Text PDFSci Rep
January 2025
School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
In this work, we synthesize a quinoline-based heptamethine cyanine, QuCy7, with sulfonate groups to enhance water solubility. This dye demonstrates exceptional near-infrared absorption beyond 750 nm, accompanied by photothermal properties but low photostability. Encapsulating QyCy7 with polyethylene glycol to form nanopolymer, QuCy7@mPEG NPs, addresses the issue of its photoinstability.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, 11884, Cairo, Egypt.
A Schiff base of Chitosan was prepared by condensing of the Chitosan (CS) with six aromatic aldehydes and confirmed by FT-IR, NMR, XRD, TGA, and DSC. XRD results showed the disappeared of peaks at 2θ = 10° for CS and appeared one peaks at around 2θ of 23° for Schiff bases, while TGA was demonstrated that the thermal stability of CS has improved after the modification with the corresponding aldehyde. Also, DSC shows endothermal peak of CS at 100 °C due to the loss of water and second thermal event related to the decomposition of amine units with an exothermic peak at 295 °C, while Schiff bases shows endothermal peak around 70-95 °C which is related to the loss of water for all samples and the second exothermic peak around 260-280 °C is related to the decomposition of the amine group in the polymer units.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, People's Republic of China
Background: Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.
Methods: In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase Aα (cPLAα), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.
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