ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
The PD-L1/4-1BB Bispecific Antibody-Anticalin Fusion Protein PRS-344/S095012 Elicits Strong T-Cell Stimulation in a Tumor-Localized Manner.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- FTL008.16, a 5T4-Conditional 4-1BB bispecific antibody, potently enhances antitumor immunity via tumor-directed t-cell activation.Oncoimmunology · 2026Article
- Review
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Clinical Development of Bispecific Antibodies: Review, Advances, and Challenges in Hematological Malignancies.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Article
- Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager.Oncoimmunology · 2025Article
- Evolution-guided design of mini-protein for high-contrastActa pharmaceutica Sinica. B · 2025Article
- CD137L promotes immune surveillance in melanoma via HLTF regulation.Nature communications · 2025Article
- The role of the transcription factor PATZ1 in tumorigenesis and metabolic regulation.Journal of cancer research and clinical oncology · 2025Review
- Advances in Antibody-Based Immune-Stimulating Drugs: Driving Innovation in Cancer Therapy.International journal of molecular sciences · 2025Review
- First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies.Journal for immunotherapy of cancer · 2025Article
- A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Bispecific immunotherapy based on antibodies, T-cell receptors, and aptamers: mechanisms of action, adverse effects, and future perspectives.Frontiers in immunology · 2025Review
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors.Molecular diagnosis & therapy · 2024Review
- Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications.Biomarker research · 2024Review
- Holistic in silico developability assessment of novel classes of small proteins using publicly available sequence-based predictors.Journal of computer-aided molecular design · 2024Article
- Bispecific antibodies for multiple myeloma: past, present and future.International journal of hematology · 2024Review
- ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1-Directed 4-1BB Activation.Cancer research · 2024Article
- Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.Antibodies (Basel, Switzerland) · 2024Article
Corrections and comments
- Commented on by
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWhile patients responding to checkpoint blockade often achieve remarkable clinical responses, there is still significant unmet need due to resistant or refractory tumors. A combination of checkpoint blockade with further T-cell stimulation mediated by 4-1BB agonism may increase response rates and durability of response. A bispecific molecule that blocks the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis and localizes 4-1BB costimulation to a PD-L1-positive (PD-L1+) tumor microenvironment (TME) or tumor draining lymph nodes could maximize antitumor immunity and increase the therapeutic window beyond what has been reported for anti-4-1BB mAbs. EXPERIMENTAL
designWe generated and characterized the PD-L1/4-1BB bispecific molecule PRS-344/S095012 for target binding and functional activity in multiple relevant in vitro assays. Transgenic mice expressing human 4-1BB were transplanted with human PD-L1-expressing murine MC38 cells to assess in vivo antitumoral activity.
resultsPRS-344/S095012 bound to its targets with high affinity and efficiently blocked the PD-1/PD-L1 pathway, and PRS-344/S095012-mediated 4-1BB costimulation was strictly PD-L1 dependent. We demonstrated a synergistic effect of both pathways on T-cell stimulation with the bispecific PRS-344/S095012 being more potent than the combination of mAbs. PRS-344/S095012 augmented CD4-positive (CD4+) and CD8-positive (CD8+) T-cell effector functions and enhanced antigen-specific T-cell stimulation. Finally, PRS-344/S095012 demonstrated strong antitumoral efficacy in an anti-PD-L1-resistant mouse model in which soluble 4-1BB was detected as an early marker for 4-1BB agonist activity.
conclusionsThe PD-L1/4-1BB bispecific PRS-344/S095012 efficiently combines checkpoint blockade with a tumor-localized 4-1BB-mediated stimulation burst to antigen-specific T cells, more potent than the combination of mAbs, supporting the advancement of PRS-344/S095012 toward clinical development. See related commentary by Shu et al., p. 3182.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.