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| Home > Publications database > The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors. |
| Home > Publications database > The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors. |
| Journal Article | DKFZ-2026-02247 |
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2026
Assoc.
Washington, DC [u.a.]
Abstract: Within solid tumors, stromal barriers and immune exclusion limit the success of immunotherapies. Thus, novel therapeutic approaches are required to remodel the tumor-supportive microenvironment and enhance therapeutic responses. We developed a bispecific, trivalent Fab-eIg T cell engager (OMTX305) targeting fibroblast activation protein (FAP), a marker of tumor-promoting cancer-associated fibroblasts. The translational potential of OMTX305 was investigated in 2D and 3D patient-derived preclinical models, with a focus on precision-cut tumor slices (PCTSs) of lung and ovarian cancer cocultured with autologous PBMCs. By combining spatial biology with cytokine and transcriptomic analysis, we show that OMTX305 treatment eliminated FAP-expressing fibroblasts, induced interferon responses and extracellular matrix remodeling, ultimately triggering bystander killing of adjacent tumor cells. Distinct immune phenotypes and PD-L1 expression patterns appeared to be associated with differential treatment responses, suggesting their potential as biomarkers for patient stratification. Our findings highlight the clinical potential of targeting stromal elements as a cancer therapy and establish PCTS as a powerful preclinical platform for personalized immunotherapy assessment.
Keyword(s): Humans (MeSH) ; Antibodies, Bispecific: pharmacology (MeSH) ; Antibodies, Bispecific: immunology (MeSH) ; Fibroblast Activation Protein Alpha (MeSH) ; Gelatinases: immunology (MeSH) ; Gelatinases: antagonists & inhibitors (MeSH) ; Gelatinases: metabolism (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: drug effects (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; CD3 Complex: immunology (MeSH) ; Membrane Proteins: antagonists & inhibitors (MeSH) ; Membrane Proteins: immunology (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Endopeptidases (MeSH) ; Tumor Microenvironment: drug effects (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Female (MeSH) ; Serine Endopeptidases: immunology (MeSH) ; Serine Endopeptidases: metabolism (MeSH) ; Ovarian Neoplasms: immunology (MeSH) ; Ovarian Neoplasms: drug therapy (MeSH) ; Ovarian Neoplasms: pathology (MeSH) ; Neoplasms: immunology (MeSH) ; Neoplasms: drug therapy (MeSH) ; Neoplasms: pathology (MeSH) ; Neoplasms: metabolism (MeSH) ; Immunotherapy (MeSH) ; Coculture Techniques (MeSH) ; Cell Line, Tumor (MeSH) ; Animals (MeSH) ; Antibodies, Bispecific ; Fibroblast Activation Protein Alpha ; Gelatinases ; CD3 Complex ; Membrane Proteins ; Endopeptidases ; Serine Endopeptidases
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