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B7-H3 (CD276), a member of the B7-family of immune checkpoint proteins, has been shown to have immunological and non-immunological effects promoting tumorigenesis [1, 2] and expression correlates with poor prognosis for many solid tumors, including cervical, ovarian and breast cancers [3-6]. We recently identified a tumor-cell autochthonous tumorigenic role for dimerization of the 4Ig isoform of B7-H3 (4Ig-B7-H3) [7], where 4Ig-B7-H3 dimerization activated tumor-intrinsic cellular proliferation and tumorigenesis pathways, providing a novel opportunity for therapeutic intervention. Herein, a live cell split-luciferase complementation strategy was used to visualize 4Ig-B7-H3 homodimerization in a high-throughput small molecule screen (HTS) to identify modulators of this protein-protein interaction (PPI).
View Article and Find Full Text PDFPotent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.
RSC Adv
January 2025
Department of Chemistry, College of Science, King Saud University P. O. Box 2455 Riyadh 11451 Saudi Arabia
The search for effective anti-cancer therapies has led to the exploration of dual inhibition strategies targeting multiple key molecular pathways. In this study, we aimed to design a novel candidate capable of dual inhibition targeting both EGFR (Epidermal Growth Factor Receptor) and PARP-1 (poly(ADP-ribose)polymerase-1), two crucial proteins implicated in cancer progression and resistance mechanisms. Through molecular hybridization and structure-based drug design approaches, we synthesized a series of compounds based on spirooxindole with triazole scaffolds with the potential for dual EGFR and PARP-1 inhibition.
View Article and Find Full Text PDFThe novel CD16A/anti-CD3 bifunctional protein, eCD16A/anti-CD3-BFP, redirects T cell cytotoxicity toward antibody-bound target cells.
Hum Vaccin Immunother
December 2025
Department of Research and Development, ManySmart Therapeutics, Taipei, Taiwan.
Monoclonal antibodies enhance innate immunity, while bispecific T cell engager antibodies redirect adaptive T cell immunity. To stimulate both innate and adaptive mechanisms, we created a bifunctional eCD16A/anti-CD3-BFP adapter protein for combined use with clinically approved monoclonal IgG1 antibodies. The adaptor protein contains the extracellular domain of the human CD16A high-affinity variant, which binds the Fc domain of IgG1 antibodies, and an anti-human CD3 single-chain variable fragment that redirects T cell cytotoxicity.
View Article and Find Full Text PDFEnhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.
Clin Transl Med
January 2025
Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Queensland, Australia.
Background: Paediatric sarcomas, including rhabdomyosarcoma, Ewing sarcoma and osteosarcoma, represent a group of malignancies that significantly contribute to cancer-related morbidity and mortality in children and young adults. These cancers share common challenges, including high rates of metastasis, recurrence or treatment resistance, leading to a 5-year survival rate of approximately 20% for patients with advanced disease stages. Despite the critical need, therapeutic advancements have been limited over the past three decades.
View Article and Find Full Text PDFDevelopment of a two-component recombinant vaccine for COVID-19.
Front Immunol
January 2025
Innovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Introduction: Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues to pose a significant threat to human society. Vaccination remains one of the most effective methods for preventing COVID-19. While most of the antigenic regions are found in the receptor binding domain (RBD), the N-terminal domain (NTD) of the S protein is another crucial region for inducing neutralizing antibodies (nAbs) against COVID-19.
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