Exploratory immunogenicity assessment
OrganoAb is developing human immune organoid studies to investigate B cell responses to therapeutic candidates. These studies are intended to complement existing immunogenicity assessment methods and support exploratory comparisons under matched conditions.
Where organoids fit
| Approach | What it measures | Uses human cells |
|---|---|---|
| In silico epitope prediction | Predicted T cell epitopes from sequence | No |
| MHC-associated peptide proteomics (MAPPs) | Peptides presented by donor antigen-presenting cells | Yes |
| PBMC and dendritic cell-T cell assays | T cell activation in response to the test article | Yes |
| OrganoAb immune organoids (in development) | Human B cell responses to the test article under matched conditions | Yes |
Anti-drug antibodies are made by B cells, so a B cell readout can complement T cell-focused methods. Clinical immunogenicity also depends on product, patient, and treatment factors, so no single preclinical readout predicts it on its own.
Exploratory study objectives
Studies are scoped around a specific question, with objectives agreed in advance.
Candidate variants
Explore differences in B cell responses between engineered variants of the same molecule.
Reference molecules
Include comparators with known clinical immunogenicity to help interpret results.
Product attributes
Investigate how factors such as aggregation affect B cell responses to a given molecule.
A study, step by step
Study design
We agree on the test articles, comparators, readouts, and the decision the study needs to inform.
Donor panel
Where donor availability and characterization allow, we select donors to represent HLA diversity, since responses to the same molecule vary between people.
Organoid exposure
Donor immune cells are cultured in organoids and exposed to each test article under matched conditions.
Readouts and report
We measure the agreed readouts, such as B cell activation and, where a drug-specific assay is established, antibodies against each test article. Results are reported by donor and across the panel.
These are exploratory, research-use studies intended to complement existing methods. B cell activation and drug-specific antibody production are distinct measurements, and neither should be read as a prediction of clinical anti-drug antibody incidence. They do not replace clinical immunogenicity testing.
Questions
Who runs the work?
Projects are designed and coordinated by the OrganoAb team, and we describe the operating plan for each project during scoping.
How many donors are in a study?
Panel size depends on the question, the number of test articles, and donor availability. We recommend a panel during study design.
Can we discuss a project confidentially?
Yes. We put a confidentiality agreement in place before any detailed discussion of your molecules or targets.