Commercial Clients' Projects

ATB19-09 - Human Kidney cells for use in drug safety studies

Many new drug molecules or new drug compounds do not reach the market because toxicity to the human kidney. This toxic effect is often not found until the compound has entered clinical trials in humans which can result in many years of wasted effort. This problem is the due to the poor predictive ability of the current tests that are used before a new compound is tested in humans. These tests often involve animal models and are poor mimics of human physiology. What is required is a better model of human kidneys to assess safety before a drug progresses to a clinical trial.

ATB20-15 - Prospective Evaluation of AI R&D tool for patient stratification (PEAR)

Pear Bio is a London-based computational biology company discovering predictive biomarkers to guide cancer treatment for improved patient outcomes. We have developed a multivariate analysis of 3D cell cultures combining primary tumours, live-cell microscopy, multi-omic readouts, and proprietary computer vision pipelines to analyse time-lapse 3D image data and quantify ex vivo cancer progression against potential treatment options. By comparing therapies side-by-side outside of the patient, the Pear Bio test enables oncologists to make better informed decisions based on personalised differential drug efficacies.

Continued collaboration with ATB has allowed Pear Bio to develop efficient cell extraction protocols from tumours, culture in microfluidics and 3D culture platforms, and dosing of various therapeutic agents. We now seek to expand collection to blood products, so that we may test immunotherapies (treatments that require the presence of immune cells, extracted from a patient’s own blood).

The workflow of Pear Bio’s device:

We culture the primary tumour cells in our proprietary 3D microtumours, which act as a physiologically-relevant proxy for the real patient tumour. The tumour cells are split among multiple 3D cultures: some are treated with approved treatments whilst others serve as negative controls. For 5 days, cells are exposed to different treatments in parallel. Every day, drugs are cleared and re-administered to simulate the drug cycles within a human body. This also allows for combination therapies to be tested. Daily confocal images are acquired in order to visualise cell viability, spread and movement inside the chips and over time. Computer vision algorithms are applied to the images to understand personalised cell behaviours and response to treatments.

ATB21-13 - Studies on isolated tissues to investigate new medicines

The tissues will be utilised in research conducted by REPROCELL on behalf the pharmaceutical industry. REPROCELL Europe Ltd is a commercial research organization founded in 2002 that specializes in the study of human tissues for testing mechanisms and efficacy of new therapeutics, usually in partnership with pharmaceutical companies investigating new drug targets or new molecules. There are an increasing number of drugs that get to the pharmacist’s shelves only to be withdrawn due to unexpected side effects. There is growing opinion that this may be due to an over-reliance on animal models at the critical stage just before clinical trials. Human tissue can provide an excellent pre-clinical screen to investigate new potential drugs and identify problems early. This can significantly reduce the risk during clinical trials and provide valuable evidence of the lack of side effects.

ATB23-03 - Modelling human adaptive immune responses with tonsil organoids

The overall purpose of this work is to use immune cells isolated from human tissue to investigate the effects of novel therapeutics on human disease and the immune system. The immune system plays a critical part in multiple disease areas including cancer, autoimmunity, inflammation, disease of the central nervous system and infection. It can play two different roles in that it can be the cause of disease but also the primary driver of a cure. This makes immunology a very exciting, but complex, area of research and companies are actively trying to find ways to supress, enhance or facilitate the immune system depending on the outcome they want to achieve.

ATB24-05 - Validation of the QST*R Assay Range using Amniotic fluid and CVS tissue

During routine pregnancy screening, many women undergo testing to screen for genetic changes which could affect the health of the unborn child - such as Edwards, Patau’s or Downs syndrome. However, many of these procedures are expensive, labour intensive and can take up to 14 days to provide a result.

Yourgene Health manufactures a range of products which detect these genetic changes using an alternative technique called QF-PCR (Quantitative Fluorescence Polymerase Chain Reaction). These products are accurate, simple to use, have reduced hands-on-time and can provide a result in a fraction of the time and expense of other established techniques. This QST*R product range is currently cleared for use by the relevant regulatory authorities in the UK and Europe. However, changes to regulatory requirements mean that we must provide additional information to maintain this status. We plan to conduct a study/studies which will demonstrate the performance of these tests on clinical samples to support this.

ATB24-07 - Mapping cell/tissue specific 3D interactions between genes and regulatory regions in order to better understand the impact of human disease variants on gene expression regulation

Genes are the blueprint for our bodies and are encoded in DeoxyriboNucleic Acid (DNA). Variants in genes or that affect their regulation can cause a wide range of conditions and affect the function of the cells and tissues that make up our bodies. DNA is organised non-randomly in 3D within the cells (in a compartment called the cell nucleus). This 3D organisation has functional consequences and regulates the expression of genes.

Variants in DNA can be inherited (i.e. passed on from parent to child) or occur spontaneously. Research studies have linked many variants to human traits including disease risk and treatment outcomes.

Most risk variants are located outside of gene encoding DNA regions & can affect the function of regulatory regions that modulate gene expression. Often these variants don’t affect the gene they are located nearest to, but ones that are further away in the linear DNA sequence, which can make identifying the genes they affect difficult. However, by mapping how DNA is organised non-randomly in 3D within the cell nucleus, it’s possible to match regulatory regions that contain disease variants to the genes they control.

Enhanc3D Genomics’ founders invented a technique to do this and published a peer reviewed paper on it, which shows that the non-random organization of DNA within the cell nuclei is cell type specific. This study proposes to map the 3D DNA organisation of different disease and treatment relevant cell types, thereby enabling the identification of target genes for different disease variants. This has the potential to uncover new insights into disease mechanisms of action, differences in individual patient treatment responses & disease progression, & help discover new therapeutic targets.

ATB24-12 - Use of Human Tissue in Vitro to evaluate the activity of candidate drugs

Agenus is conducting R&D activities in the field of cancer immunotherapy. Their goal is to identify and bring to the patients new drugs or combinations of drugs enhancing the response of the immune system against tumour cells. To identify such drugs, they generate panels of molecules able to modulate the activity of specific targets present on immune cells. Human tissue samples (healthy or diseased) will be used to further evaluate the activity of our drug candidates.

In the present study they will access anonymised tissue samples from NHS Blood & Transplant, hospital Tissue Banks and sample archives or commercial suppliers.

Samples are for in vitro testing only. The tissues or tissue products may be stored onsite in a dedicated space prior to being used in assays. They will then be discarded according to HTA guidelines.

ATB24-17 - Identification of novel disease targets for the development of cancer immunotherapy

The aim of this project is to identify new cancer targets that can be used to aid the development of new cancer treatment. Current standard-of-care cancer therapies have moderate success rates and almost universally cause severe side effects. Such adverse effects are largely due to the imprecise ways in which these therapies work, where the drugs attack not only cancer cells but also the surrounding normal, healthy tissues. In this proposed project, Etcembly intends to discover new drug targets that are unique to cancer cells (not present on healthy cells). These targets could then assist with the design of drug candidates that are specific to them. Such a treatment strategy would mitigate the side effects seen in current treatment regimes, leading to the development of a new generation of drugs that would prove beneficial to patients.

ATB24-24 - Characterization of peripheral innate immune cell populations in colorectal as well as head and neck cancer patient samples

Patients with solid tumor cancers such as colorectal and head and neck do not have many treatment options and have poor prognosis with current drugs. One of the potential reasons for this is that the tumor microenvironment (TME) contains large numbers of innate immune cells. These cells enter the tumor from the circulation and can suppress the body’s ability to fight and clear the tumor. We have established conditions using healthy donor whole blood that model the movement into the TME and subsequent activation of innate immune cells. However, the blood of from patients with colorectal and head and neck cancers differs from that of healthy donors. The samples accessed with this application will be utilized to ensure that our potential new-drug can block the infiltration and activation of innate immune cells from patient samples. This will build confidence in the drug and support its advance towards patients.

ATB25-03 - Further development of a lymphoid model on a chip to recapitulate human immunogenicity

Monoclonal antibody (mAb) therapies are a type of targeted drug therapy that use laboratory-produced antibodies to treat diseases like cancer. They can work in different ways, such as blocking cell growth, triggering cell death, or enhancing the immune system's response. Determining the risk of these therapies often relies on initial toxicology studies in mice. Unfortunately, the results of these studies do not always produce the same response in humans. Therefore, testing these therapies in a more relevant human system would be preferable. We propose to isolate cells from human tonsils hours after surgery and culture them in a more suitable environment to determine if there is an immune response risk of new therapies in a human system prior to clinical trials. In addition, this model will reduce the need to use animals for these studies and supports the 3Rs principles (Replacement, Reduction, and Refinement in animal research).