ReviewBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2021
Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.
Review in BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Efficacy and safety of subcutaneous versus intravenous administration of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.Advances in therapy · 2025Trial
- Ozanimod as a novel oral small molecule therapy for the treatment of Crohn's disease: The YELLOWSTONE clinical trial program.Contemporary clinical trials · 2022Trial
- Immune tolerance platforms to mitigate unwanted immune responses.Journal of pharmaceutical sciences · 2026Review
- Potential Mechanisms of Partial/Transient Response or Resistance to Daratumumab Therapy: A Focus on Anti-Daratumumab Antibodies and Urinary Daratumumab Loss.Antibodies (Basel, Switzerland) · 2026Review
- Systemic pathways linking subcutaneous therapies to gastrointestinal adverse effects: A Narrative review of mechanisms and mitigation strategies.Indian journal of pharmacology · 2026Review
- Protein Delivery Using Three-Dimensional Printing of Buccal Films: Technological Advances and Clinical Potential.Pharmaceutics · 2026Review
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Engineered Escherichia coli as a microbial cell factory for intracellular protein delivery: strains, vectors, mechanisms, and therapeutic applications.Microbial cell factories · 2026Review
- The immunogenicity database collaborative: a standardized, publicly available database for clinical immunogenicity observations and insights.Frontiers in immunology · 2026Article
- Bispecific antibodies in metastatic castration-resistant prostate cancer: therapeutic strategies and frontier advances.World journal of urology · 2025Review
- Association of Immunogenicity and Drug Exposure and the Importance of Target Engagement in ADA Development: A Clinical Case Study of Anti-SARS-CoV-2 Biotherapeutics.The AAPS journal · 2025Article
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Evaluating the Immunogenicity Risk of Protein Therapeutics by Augmenting T Cell Epitope Prediction with Clinical Factors.The AAPS journal · 2025Article
- Nonshrinkable Thermosensitive Hydrogels Combined with Bispecific Anti-PSMA/CD3 T-Cell Engager for Effective Against Tumors in Mice Model.International journal of nanomedicine · 2025Article
- Review
- One SQ HEDGES DNA vector only dose produces durable hGLA or anti-SARS-CoV-2 mAb therapeutic serum protein levels.PloS one · 2025Article
- Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Designing for medication adherence in inflammatory bowel disease: multi-disciplinary approaches for self-administrable biotherapeutics.EClinicalMedicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The subcutaneous route of administration has provided convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion, but there is potential for enhanced immunogenicity toward subcutaneously administered proteins in a subset of patients. Unwanted anti-drug antibody response toward proteins or monoclonal antibodies upon repeated administration is shown to impact the pharmacokinetics and efficacy of multiple biologics. Unique immunogenicity challenges of the subcutaneous route have been realized through various preclinical and clinical examples, although subcutaneous delivery has often demonstrated comparable immunogenicity to intravenous administration. Beyond route of administration as a treatment-related factor of immunogenicity, certain product-related risk factors are particularly relevant to subcutaneously administered proteins. This review attempts to provide an overview of the mechanism of immune response toward proteins administered subcutaneously (subcutaneous proteins) and comments on product-related risk factors related to protein structure and stability, dosage form, and aggregation. A two-wave mechanism of antigen presentation in the immune response toward subcutaneous proteins is described, and interaction with dynamic antigen-presenting cells possessing high antigen processing efficiency and migratory activity may drive immunogenicity. Mitigation strategies for immunogenicity are discussed, including those in general use clinically and those currently in development. Mechanistic insights along with consideration of risk factors involved inspire theoretical strategies to provide antigen-specific, long-lasting effects for maintaining the safety and efficacy of therapeutic proteins.
Indexed as
Identifiers
What Socratic 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 Socratic graph.