Company insight
The immune system’s unwanted response
As gene therapies advance, immune reactions remain a major hurdle. Mimotopes provides high- quality peptides that help researchers predict, measure and mitigate these risks – making them essential tools for developing safer, more effective treatments.
ene therapies often use viral vectors (like AAV) to deliver a corrective transgene. While the goal is a long-lasting therapeutic effect, the body’s immune system can see the vector or even the new protein it produces as foreign. This can lead to: ■
G
immune responses against the vector, preventing re-dosing and potentially causing toxicity
■
immune responses against the transgene product, undermining the therapy’s efficacy and safety
This is where peptides become critical tools.
Key applications of peptides in gene therapy development Peptides are short chains of amino acids that mimic specific parts of proteins. This allows scientists to dissect and study immune responses with high precision.
1. Immunogenicity and immunotoxicity assessment This is the most critical application. Peptides are used to map and measure unwanted immune responses: ■
staining): Peptide pools are essential reagents in assays to monitor T-cell activation (e.g., IFN- release) in clinical trials. This is vital for patient safety monitoring.
2. Development of critical assay reagents
Peptides are essential for developing the analytical tools needed to study the therapy: ■
Why quality and expertise matter For these critical studies, the quality of the peptides is non-negotiable. Inconsistent purity, incorrect sequences or impurities can lead to false positives or negatives, jeopardising the entire development programme.
Anti-drug antibody (ADA) assays: If a patient develops antibodies against the gene therapy vector or transgene, it can neutralise the treatment. Peptides are used as positive controls or as capture/detection reagents in ADA assays to monitor this humoral immune response.
■
PK/PD assays: Peptides that mimic specific regions of the transgene
This is where Mimotopes’ 30 years of experience is crucial. Gene therapy companies need a partner that guarantees key points: ■
■
High purity: essential for specific, interpretable results in sensitive bioassays
Reliability and consistency: batch- to-batch reproducibility is vital for long-term studies and clinical trials
■
Expert support: experience in designing complex peptide pools (e.g., spanning an entire AAV serotype capsid) and scaling up synthesis for late-stage development
“Peptides are the essential tools that allow you to de-risk development by precisely characterising and mitigating immunogenic risks.”
T-cell epitope mapping: Researchers use overlapping peptides (15–20 amino acids long) that span the entire sequence of the viral capsid (e.g., AAV capsid proteins) or the therapeutic transgene product. By exposing immune cells from preclinical models or patients to these peptide pools, they can identify exactly which regions are triggering T-cell responses. This helps to predict potential immunotoxicity early in development and engineer safer next-generation vectors by modifying immunodominant epitopes (‘de-immunisation’).
■
Monitoring immune responses (ELISPOT, intracellular cytokine
www.worldpharmaceuticals.net
product can be used to generate antibodies for quantifying protein expression levels (pharmacokinetics) and demonstrating biological activity (pharmacodynamics).
3. Downstream applications: purification and characterisation ■
Affinity purification ligands: Custom peptides can be designed to mimic receptor binding sites and used to create resins for purifying the gene therapy product.
■
Mass spectrometry standards: Synthetic peptides with stable isotopes are used as internal standards to accurately quantify protein expression levels using mass spectrometry.
Summary for messaging In gene therapy, safety is paramount. Peptides are the essential tools that allow you to de-risk development by precisely characterising and mitigating immunogenic risks. They are the key to understanding immune responses against your vector and transgene, enabling you to build a stronger safety profile and increase the chances of clinical success. Partnering with an experienced peptide provider ensures these critical reagents are of the highest quality, giving you confidence in your data. This positions Mimotopes not just as a supplier, but as a strategic partner in developing safer and more effective gene therapies. ●
https://mimotopes.com 75
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85
