The HuLOr study
Research type
Research Study
Full title
Human Lymphoid Organoid modelling
IRAS ID
348592
Contact name
Eoin McKinney
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Clinicaltrials.gov Identifier
A097110, CUH R&D number
Duration of Study in the UK
5 years, 5 months, 30 days
Research summary
While studies in humans are best placed to evaluate the impact of an intervention to modulate immune responses, it is necessary to have a means of investigating mechanism. This can't easily be done in people and requires a form of 'model system'. Ideally this model system would recapitulate key features of a human immune response but be open to manipulation with drugs, genetic or cellular alterations.
Establishing a model immune system ('organoid') requires that human immune cells are obtained from lymphoid tissue (specialised immune t, then cryopreserved before stimulation with antigen, driving formation of germinal-centre responses and mature antibody and cellular responses, similar to those generated in vivo.
This experimental system can be used to compare immune responses between donors of different ages and those generated by cells from a given individual with/without intervention. Interventions can be in the form of specific treatment (e.g. an individual drug or knockdown of a specific gene) or using unbiased high-throughput modification of multiple gene targets (e.g. using CRISPR-Cas9 modulation). f
We propose to set up a model immune system to investigate the impact of interventions on the outcome of immune responses.
We will use an established method where human immune cells from tonsils or spleen tissue form into organoids capable of responding to challenge (like vaccination) and retain all the hallmarks of adaptive immunity to vaccine responses. These organoid cultures can also be manipulated to test the impact of different interventions.
Organoids derived from human tonsil, spleen or lymph nodes will be challenged with standardised immunogen (e.g. influenza/SARS-CoV2 vaccine) and we will investigate the effects of candidate molecules or interventions on organoid function.REC name
North West - Liverpool Central Research Ethics Committee
REC reference
25/NW/0069
Date of REC Opinion
6 Mar 2025
REC opinion
Favourable Opinion