Bifunctional Phagocytic Synapse Enhancers for Cancer Immunotherapy
Sabatino, V.; Fleisch, S.; Tang, C.; Muller, F. M.; Labao-Almeida, C.; Khaw, W. T.; Hogan, S.; Hicks, D. R.; Fontes, M.; Coelho, A. R.; Yang, W.; Sarkar, I.; Shome, D.; Vidal, A. V.; Cabeza-Cabrerizo, M.; Rohm, T.; Reijmers, R. M.; Kaymak, D.; Gerster, F.; Baker, D.; Fior, R.; Hutter, G.; Bernardes, G. J. L.
Show abstract
Immunotherapy profoundly impacted cancer treatments by harnessing the patients immune system. Phagocytosis, the process whereby immune cells engulf and destroy foreign particles or cells, plays a critical role in tumour cell clearance. Herein, we introduce a novel concept termed "ENPHASYS" - Enhancement of Phagocytic Synapses - designed to direct and amplify phagocytosis of cancer cells using heterobifunctional molecules named phagocytic synapse enhancers (PSEs). By engineering a de novo PD-L1 binder linked to a natural phagocytosis promoting peptide, tuftsin, the resulting PSE combines PD-L1 blockade with enhanced tumour cell phagocytosis; in addition, the PSEs induce macrophages to internalize a membrane or extracellular target. Intratumoural treatment of colorectal carcinoma- or glioblastoma-burdened immunocompetent animals resulted in beneficial overall survival, delayed tumour growth and a potent antitumor response driven by T-cell activation and TAM reprogramming, underpinning the translational relevance of ENPHASYS. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/642658v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1673fd4org.highwire.dtl.DTLVardef@18fa319org.highwire.dtl.DTLVardef@11cf680org.highwire.dtl.DTLVardef@7b8784_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Immunofilaments Provide a Nanoscale Platform for In Vivo T Cell Expansion and Cancer Immunotherapy 97%
- SARS-CoV-2 B Epitope-Guided Neoantigen NanoVaccines Enhance Tumor-Specific CD4/CD8 T Cell Immunity Through B Cell Antigen Presentation 96%
- Multivalent, Bispecific ????B7-H3-????CD3 Chemically Self-Assembled Nanorings Direct Potent T-cell Responses Against Medulloblastoma 95%
Similar papers in this journal
Similar papers in this journal
- Neutrophil Extracellular Trap gene expression signatures identify prognostic and targetable signaling axes for inhibiting metastasis of pancreatic tumours 95%
- In-cell proximity target validation methods for heterobifunctional molecules with CRBN- or VHL-binder using AirID 95%
- LRRK2-mutant microglia and neuromelanin synergize to drive dopaminergic neurodegeneration in an iPSC-based Parkinson's disease model 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.