New therapy concept for hodgkin lymphoma: CD86 revealed as a weak point

Hodgkin's lymphoma is a form of lymph gland cancer. Children and young adults are particularly frequently affected. Researchers at the LMU Hospital in Munich have discovered a potential new weak point in Hodgkin's lymphoma: the CD86 molecule. With the help of AI, they have developed novel immunotherapies that could be more targeted and less aggressive than previous treatments - a glimmer of hope for young patients. The study was published in the scientific journal ‘Blood’.

Around one in seven children with a malignant tumour has Hodgkin's lymphoma. The disease also frequently occurs in young adults. It is one of the cancers with the highest cure rates, with over 90 per cent of those affected surviving in the long term following aggressive, high-dose chemotherapy.

However, many of the cured children and young adults have to contend with late effects in the course of their lives. These can be minor complications, such as hormonal imbalances or an increased susceptibility to infections. But they can also be serious illnesses, such as a recurrence of cancer or heart or lung failure.

‘The need for new, less aggressive therapies that act as specifically as possible on the cancer cells and the surrounding tumour environment is therefore very great,’ says Dr Adrian Gottschlich, first author of the study. Especially as Hodgkin's lymphomas build up an environment around the actual cancer cells that suppresses any activity of the immune system against the tumour particularly strongly and ‘reprograms’ immune cells for its growth.

Researchers at LMU Hospital led by Dr Adrian Gottschlich and Prof. Dr Sebastian Kobold, both scientists in the German Consortium for Translational Cancer Research (DKTK) at the partner site in Munich, have developed new immunotherapies for patients with Hodgkin's lymphoma in the laboratory. In other words, they could attack the tumour from different angles.

The team led by the Munich physicians has created the experimental prerequisites for new targeted therapies. The focus: a molecule called CD86. ‘With the help of artificial intelligence,’ explains Prof. Sebastian Kobold, ‘we were able to identify CD86 as a central control element in the tumour environment of Hodgkin's lymphomas, which protects the cancer cells from the immune system.’

The molecule is found both on the surface of the tumour cells themselves and on the surface of certain immune cells (phagocytes) that migrate into the cancer and support its growth instead of fighting it.

Drugs that stimulate the immune system and kill cancer cells

In order to prevent the fatal effect of CD86, the researchers blocked the molecule in a targeted manner and were thus able to abolish the dormant state of T cells, which emphasises the central importance of CD86 in the inhibition of these immune cells. In parallel, the team developed a CAR T cell therapy against CD86. ‘These anti-CD86 CAR T cells,’ reports Gottschlich, ‘showed outstanding efficacy in numerous disease models.’

The results make CD86 a promising target structure for new therapies against Hodgkin's lymphoma in humans. The Munich scientists are already working intensively on the production of anti-CD86 CAR T cells for use in a clinical trial.

This is no easy endeavour, as it requires various components and partners as well as the necessary funds. 'What's more,' says Kobold, "our research could introduce a new generation of immune checkpoint inhibitors. These drugs could then not only reactivate the immune system - as is currently the case - but also kill the cancer cells directly."

Source: DKTK (in German)