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Neoantigen-Displaying Protein Nanoparticles as a Therapeutic Cancer Vaccine Against Melanoma.
Adv Healthc Mater
December 2024
Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Although interest in peptide-based cancer vaccines has surged in the era of personalized immunotherapy enabled by the discovery of neoantigens, the effective generation of neoantigen-specific T cell responses has been limited. Here, a Brucella BP26 protein-based nanoparticle displaying the MHC class II-restricted melanoma neoantigen, M30, is reported for use as a therapeutic cancer vaccine. Genetic engineering of 10 tandem repeats of the M30 neoepitope to a BP26 monomer results in the self-assembled, neoantigen-displaying protein nanoparticles (BP26-M30 NPs).
View Article and Find Full Text PDFPhosphopeptide Neoantigens as Emerging Targets in Cancer Immunotherapy.
J Cancer Immunol (Wilmington)
January 2024
Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Protein post-translational modifications play a vital role in various cellular events essential for maintaining cellular physiology and homeostasis. In cancer cells, aberrant post-translational modifications such as glycosylation, acetylation, and phosphorylation on proteins can result in the generation of antigenic peptide variants presented in complex with MHC molecules. These modified peptides add to the class of tumorspecific antigens and offer promising avenues for targeted anti- cancer therapies.
View Article and Find Full Text PDFRadioimmunotherapy: a game-changer for advanced non-small cell lung cancer.
Front Immunol
December 2024
Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related deaths, with conventional treatments offering limited effectiveness in advanced stages, due to distant metastases and treatment resistance. Recent advancements in immunotherapy, specifically immune checkpoint inhibitors (ICIs), have shown promise, but their efficacy as standalone therapies are often insufficient. This has led to increased interest in combining ICIs with radiotherapy, known as radioimmunotherapy (iRT), to enhance treatment outcomes.
View Article and Find Full Text PDFAntigen presentation by MHC-II is shaped by competitive and cooperative allosteric mechanisms of peptide exchange.
Structure
December 2024
Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address:
Major histocompatibility complex class II (MHC-II) presents antigens to T helper cells. The spectrum of presented peptides is regulated by the exchange catalyst human leukocyte antigen DM (HLA-DM), which dissociates peptide-MHC-II complexes in the endosome. How susceptible a peptide is to HLA-DM is mechanistically not understood.
View Article and Find Full Text PDFMultimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.
Cancer Discov
December 2024
Brigham and Women's Hospital, Boston, MA, United States.
High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC.
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