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Published: 11 September 2024

Roche uses non-animal methods to improve drug development

Immune cells are not only found in the blood but also in tissues. For example, in the intestine, there are so-called memory T cells that can respond quickly in the event of an infection. However, sometimes the reaction of immune cells is undesirable, such as in the case of side effects from medications. Until now, such effects could not be studied using organoids, as they lacked immune cells. Now, scientists from the Roche Institute of Human Biology (IHB) and the R&D department of the pharmaceutical company have developed an innovative human intestinal organoid model that also includes immune cells.

In the study recently published in the renowned journal Nature, the researchers used intestinal tissue from patients who had part of their intestines removed during medically necessary surgery. From the intestinal tissue, the researchers isolated memory T cells and grew intestinal organoids – small three-dimensional cell constructs – from the mucosal cells. They then combined the immune cells with the organoids and observed how the T cells distributed themselves on and within the organoids – similar to the situation in the human gut (1).

The researchers demonstrated how these intestinal organoids can be used to understand immune system-related side effects of medications. For this purpose, they used Solitomab, an antibody developed for cancer therapy. However, in clinical trials, the antibody caused severe side effects, including intestinal inflammation. The mechanism by which Solitomab leads to intestinal inflammation was previously unclear and could now be investigated using the novel organoids.

The drug-induced intestinal inflammation could be reduced in the organoid model using therapeutic antibodies that are also used for autoimmune diseases. Additionally, a compound that reduces the mobility of T cells was able to alleviate the inflammation. Thus, the organoids helped to clarify the mechanism of drug-induced intestinal inflammation and identify potential treatment approaches. Using the organoids before clinical trials in humans could have enabled the early detection and avoidance of such side effects.

It is expected that the intestinal organoids can also be used to study infections, colorectal cancer, and autoimmune diseases. Additionally, the researchers at the IHB plan to extend the concept to other organs, for example, by incorporating immune cells into lung organoids (2).

The results demonstrate the potential of organoids to detect and understand not only the effects but also the side effects of drugs at an early stage – by directly using human material. This can increase the success of future medications. This is also the stated goal of the IHB, which aims to improve drug development and make it more efficient. To achieve this, the IHB does not use animal testing but modern human-based models such as human organoids or innovative computer models (3).