ArticleCancer immunology, immunotherapy : CII2020
Development of CDX-527: a bispecific antibody combining PD-1 blockade and CD27 costimulation for cancer immunotherapy.
Article in Cancer immunology, immunotherapy : CII, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Agonistic bispecific antibodies: an emerging frontier in antibody therapeutics.Journal of translational medicine · 2026Review
- Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation.Cancer chemotherapy and pharmacology · 2026Review
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- A hexamerization-enhanced, Fc-silenced agonistic CD27 antibody amplifies T-cell effector functions as single agent and in combination with PD-1 blockade.Scientific reports · 2025Article
- Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors.Molecular diagnosis & therapy · 2024Review
- Bispecific and multispecific antibodies in oncology: opportunities and challenges.Nature reviews. Clinical oncology · 2024Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Anti-Tumor Potential of Post-Translational Modifications of PD-1.Current issues in molecular biology · 2024Review
- Differences in Co-Expression of T Cell Co-Inhibitory and Co-Stimulatory Molecules with PD-1 Across Different Human Cancers.Journal of oncology research and therapy · 2024Article
- Potential therapeutic targets for membranous nephropathy: proteome-wide Mendelian randomization and colocalization analysis.Frontiers in immunology · 2024Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment.Cancers · 2023Review
- Targeting tumor microenvironment for non-small cell lung cancer immunotherapy.Chinese medical journal pulmonary and critical care medicine · 2023Review
- Friend or Foe - Tc17 cell generation and current evidence for their importance in human disease.Discovery immunology · 2023Review
- EGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells.Frontiers in immunology · 2023Article
- Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.Molecular cancer · 2022Review
- The PD-1 Interactome.Advanced biology · 2021Review
- Mechanism of action of PD-1 receptor/ligand targeted cancer immunotherapy.European journal of immunology · 2021Review
- Targeting the CD27-CD70 Pathway to Improve Outcomes in Both Checkpoint Immunotherapy and Allogeneic Hematopoietic Cell Transplantation.Frontiers in immunology · 2021Review
- Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival.Frontiers in medicine · 2021Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD27 is a costimulatory molecule that provides a complementary target to the PD-1/PD-L1 checkpoint axis on T cells. Combining a CD27 agonist antibody with PD-1/PD-L1 blockade has shown synergistic antitumor activity in preclinical models, which led to clinical studies of the combination in cancer patients. We theorized that coupling CD27 costimulation with PD-1/PD-L1 blockade in a bispecific antibody (BsAb) may provide greater immune activating properties than combining the individual mAbs due to enhanced CD27 activation by cross-linking through PD-L1 and Fc receptors. To test this approach, we developed CDX-527, a tetravalent PD-L1xCD27 IgG1-scFv BsAb. CDX-527 potently inhibits PD-1 signaling and induces CD27-mediated T cell costimulation through PD-L1 cross-linking. In mixed lymphocyte reaction assays, CDX-527 is more potent than the combination of the parental antibodies, suggesting that cross-linking through both Fc receptors and PD-L1 results in enhanced CD27 agonist activity. CDX-527 was shown to mediate effector function against tumor cells overexpressing either CD27 or PD-L1. In human CD27 transgenic mice, we observed that antigen-specific T cell responses to a vaccine are greatly enhanced with a surrogate PD-L1xCD27 BsAb. Furthermore, the BsAb exhibits greater antitumor activity than the combination of the parental antibodies in a syngeneic lymphoma model. A pilot study of CDX-527 in cynomolgus macaques confirmed a mAb-like pharmacokinetic profile without noted toxicities. These studies demonstrate that CDX-527 effectively combines PD-1 blockade and CD27 costimulation into one molecule that is more potent than combination of the parental antibodies providing the rationale to advance this BsAb toward clinical studies in cancer patients.
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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.