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Structure and dynamics of monoclonal antibody domains determined using spins, scattering, and simulations.
ChemMedChem
January 2025
National Institute of Standards and Technology, Material Measurement Laboratory, UNITED STATES OF AMERICA.
Antibody-based pharmaceuticals are the leading biologic drug platform (> $75B/year). Despite a wealth of information collected on them, there is still a lack of knowledge on their inter-domain structural distributions, which impedes innovation and development. To address this measurement gap, we have developed a new methodology to derive biomolecular structure ensembles from distance distribution measurements via a library of tagged proteins bound to an unlabeled and otherwise unmodified target biologic.
View Article and Find Full Text PDFFAP-targeted radioligand therapy with Ga/Lu-DOTA-2P(FAPI) enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy.
J Immunother Cancer
January 2025
Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Background: Fibroblast activation protein (FAP)-targeted radioligand therapy, with immunomodulatory effects, has shown efficacy in both preclinical and clinical studies. We recently reported on a novel dimeric FAP-targeting radiopharmaceutical, Ga/Lu-DOTA-2P(FAPI), which demonstrated increased tumor uptake and prolonged retention in various cancers. However, further exploration is required to understand the therapeutic efficacy and underlying mechanisms of combining Ga/Lu-DOTA-2P(FAPI) radioligand therapy with PD-1/PD-L1 immunotherapy.
View Article and Find Full Text PDFThe Relationship Between Impulsivity Traits and In Vivo Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in Healthy Individuals: A Double-Tracer PET Study with C-11 DASB and C-11 MDL100907.
Int J Mol Sci
December 2024
Neuroscience Research Institute, Gachon University, Incheon 21565, Republic of Korea.
To elucidate the potential roles of presynaptic and postsynaptic serotonergic activity in impulsivity traits, we investigated the relationship between self-reported impulsiveness and serotonin transporter (5-HTT) and 5-HT2A receptors in healthy individuals. In this study, 26 participants completed 3-Tesla magnetic resonance imaging and positron emission tomography with [C]DASB and [C]MDL100907. To quantify 5-HTT and 5-HT2A receptor availability, the binding potential (BP) of [C]DASB and [C]MDL100907 was derived using the simplified reference tissue model with cerebellar gray matter as the reference region.
View Article and Find Full Text PDFDarolutamide in Combination with Radium-223 Exhibits Synergistic Antitumor Efficacy in LNCaP Prostate Cancer Models.
Int J Mol Sci
December 2024
Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany.
Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone.
View Article and Find Full Text PDFTargeting mutant p53: Evaluation of novel anti-p53 monoclonal antibodies as diagnostic tools.
Sci Rep
January 2025
Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 (p53 in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 could prove immensely value.
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