CD86: Target of new therapies against Hodgkin's lymphoma

Hodgkin's lymphoma is a form of lymph node cancer. It occurs particularly frequently in children and young adults. Researchers at LMU Hospital from Medical Clinic III and the Department of Clinical Pharmacology at LMU Hospital, led by Dr. Adrian Gottschlich and Prof. Dr. Sebastian Kobold, have now developed new immunotherapies for patients with Hodgkin's lymphoma in the laboratory. These therapies could attack the tumor from different angles, so to speak. The groundbreaking study was published in the journal "Blood."

Approximately one in seven children with a malignant tumor 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 percent of those affected surviving in the long term thanks to aggressive, high-dose chemotherapy.

However, many of the children and young adults who have been cured struggle with long-term effects throughout their lives. These can be minor complications, such as hormonal imbalances or increased susceptibility to infection. But they can also be serious illnesses, such as recurrent cancer or heart or lung failure. "There is therefore a great need for new, less aggressive therapies that target the cancer cells and the surrounding tumor environment as precisely as possible," says Dr. Adrian Gottschlich, lead author of the study. This is especially true since Hodgkin's lymphomas build up an environment around the actual cancer cells that strongly suppresses any activity of the immune system against the tumor and "reprograms" immune cells for its growth.

A team led by Munich-based physicians has now created the experimental conditions for new targeted therapies. The focus is on 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 tumor environment of Hodgkin's lymphomas that protects cancer cells from the immune system." The molecule is found both on the surface of the tumor cells themselves and on the surface of certain immune cells (phagocytes) that migrate into the cancer and support its growth instead of fighting it.

Medications that stimulate the immune system and kill cancer cells

To prevent the fatal effect of CD86, the researchers specifically blocked the molecule, thereby reversing the dormant state of T cells, which underscores the central importance of CD86 in inhibiting these immune cells. At the same time, the team developed a CAR-T cell therapy against CD86. "These anti-CD86 CAR-T cells," reports Gottschlich, "demonstrated outstanding efficacy in numerous disease models."

The results make CD86 a promising target structure for new therapies against Hodgkin's lymphoma in humans as well. The Munich-based scientists are already working intensively on the production of anti-CD86 CAR-T cells for use in a clinical trial. This is no easy task, as it requires various components, partners, and the necessary funds. "In addition," says Kobold, "our research could usher in a new generation of immune checkpoint inhibitors. These drugs could then not only reactivate the immune system—as has been the case up to now—but also kill the cancer cells directly."

Original publication:
Adrian Gottschlich, Ruth Grünmeier, […] Michael von Bergwelt-Baildon, Paul J. Bröckelmann, Stefan Endres, Sebastian Kobold; Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma. Blood 2025; 145 (14): 1536–1552. doi: https://doi.org/10.1182/blood.2023022197