ArticleNature communications2022
The engineered CD80 variant fusion therapeutic davoceticept combines checkpoint antagonism with conditional CD28 costimulation for anti-tumor immunity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 58 citations in OpenAlex.
- Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- CD80-Mediated T-Cell Suppression by Cancer Stem-like Cells in Head and Neck Squamous Cell Carcinoma.Cells · 2026Article
- Recombinant human adenovirus type 5 synergizes with anti-PD-L1 antibody to promote anti-hepatocellular carcinoma effects through multilevel remodeling of the immune microenvironment.Frontiers in immunology · 2026Article
- From tumor immunotherapy to myocardial injury: A mechanistic discussion of immune checkpoint inhibitor‑related myocarditis (Review).Molecular medicine reports · 2025Review
- Surface Plasmon Resonance (SPR)-Based Workflow for High-Throughput Discovery of CD28-Targeted Small Molecules.ACS omega · 2025Article
- CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting.Bioorganic & medicinal chemistry letters · 2025Review
- Investigation of the CTLA-4-CD28 Axis in Oral Squamous Cell Carcinoma.Journal of clinical medicine · 2025Article
- Spatial and stoichiometric in situ analysis of biomolecular oligomerization at single-protein resolution.Nature communications · 2025Article
- Targeting HMGB2 acts as dual immunomodulator by bolstering CD8Science advances · 2025Article
- Tumor cells ectopically expressing the membrane-bound form of IL-7 develop an antitumor immune response efficiently in a colon carcinoma model.Molecules and cells · 2025Article
- Overcoming resistance to PD-1 and CTLA-4 blockade mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
- Rigid, bivalent CTLA-4 binding to CD80 is required to disrupt the cis CD80/PD-L1 interaction.Cell reports · 2024Article
- Phase I studies of davoceticept (ALPN-202), a PD-L1-dependent CD28 co-stimulator and dual PD-L1/CTLA-4 inhibitor, as monotherapy and in combination with pembrolizumab in advanced solid tumors (NEON-1 and NEON-2).Journal for immunotherapy of cancer · 2024Article
- A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumor immune.Journal of nanobiotechnology · 2024Article
- Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease.Journal for immunotherapy of cancer · 2024Article
- Review
- CD80-Fc fusion protein as a potential cancer immunotherapy strategy.Antibody therapeutics · 2024Review
- Review
- Structural and biological characterization of pAC65, a macrocyclic peptide that blocks PD-L1 with equivalent potency to the FDA-approved antibodies.Molecular cancer · 2023Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the recent clinical success of T cell checkpoint inhibition targeting the CTLA-4 and PD-1 pathways, many patients either fail to achieve objective responses or they develop resistance to therapy. In some cases, poor responses to checkpoint blockade have been linked to suboptimal CD28 costimulation and the inability to generate and maintain a productive adaptive anti-tumor immune response. To address this, here we utilize directed evolution to engineer a CD80 IgV domain with increased PD-L1 affinity and fuse this to an immunoglobulin Fc domain, creating a therapeutic (ALPN-202, davoceticept) capable of providing CD28 costimulation in a PD-L1-dependent fashion while also antagonizing PD-1 - PD-L1 and CTLA-4-CD80/CD86 interactions. We demonstrate that by combining CD28 costimulation and dual checkpoint inhibition, ALPN-202 enhances T cell activation and anti-tumor efficacy in cell-based assays and mouse tumor models more potently than checkpoint blockade alone and thus has the potential to generate potent, clinically meaningful anti-tumor immunity in humans.
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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.