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Evaluating the Immunogenicity Risk of Protein Therapeutics by Augmenting T Cell Epitope Prediction with Clinical Factors.
AAPS J
January 2025
Department of BioAnalytical Sciences, Genentech Inc, South San Francisco, California, USA.
Protein-based therapeutics may elicit undesired immune responses in a subset of patients, leading to the production of anti-drug antibodies (ADA). In some cases, ADAs have been reported to affect the pharmacokinetics, efficacy and/or safety of the drug. Accurate prediction of the ADA response can help drug developers identify the immunogenicity risk of the drug candidates, thereby allowing them to make the necessary modifications to mitigate the immunogenicity.
View Article and Find Full Text PDFFirst-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies.
J Immunother Cancer
January 2025
Department of Oncology, Uppsala University Hospital, Uppsala, Sweden
Background: ATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cell death.
Methods: In this first-in-human, multicenter, phase I study, ATOR-1017 was administered intravenously every 21 days as a monotherapy to patients with advanced, unresectable solid tumors having received multiple standard-of-care treatments.
PD-1 cis-targeted IL-2v in combination with radiotherapy inhibits lung cancer growth and remodels the immune microenvironment.
J Immunother Cancer
January 2025
Route de la Corniche 3B, Novigenix SA, 1066, Epalinges, Switzerland
Background: More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model of metastatic lung adenocarcinoma (SV2-OVA) to assess the safety and efficacy of novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine and muFAP-CD40 bispecific antibody.
Methods: We evaluated the changes in the lung immune microenvironment at multiple timepoints following combination therapies and investigated their underlying antitumor mechanisms.
Lipid-Rapamycin Nanovaccines Overcome the Antidrug Antibody Barrier in Biologic Therapies.
ACS Nano
January 2025
Wuya Faculty of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Antidrug antibodies (ADAs) against biologics present a major challenge for sustained biotherapy, including enzyme replacement therapies and adeno-associated virus (AAV) gene therapies. These antibodies arise from undesirable immune responses, leading to altered pharmacokinetics, reduced efficacy, and adverse reactions. In this study, we introduced a rationally designed lipid-rapamycin (Rapa)-based nanovaccine to restore immune tolerance to biologics and overcome drug resistance.
View Article and Find Full Text PDFEpstein-Barr virus BALF0/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation.
Proc Natl Acad Sci U S A
January 2025
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Epstein-Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane (PM) B cell receptor (BCR) complexes, composed of immunoglobulin and the CD79A and CD79B signaling chains.
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