Research Links Protein to Immune Response to Cancer

Researchers from the from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Germany have discovered that shutting down the EBAG9 gene in mice led to a sustained increase in the immune response to cancer. The mice also developed more T memory cells, which allows the immune system to respond better to a cancer antigen after encountering it previously.

The research was published last month in the journal JCI Insight by a team led by authors Dr Armin Rehm and Dr Uta Höpken from the MDC. Now the researchers have also shown these key findings in vitro, in human chimeric antigen receptor T cells (CAR T cells) cells. Writing in Molecular Therapy, the team says that this is the decisive step on the road to therapeutic use. “Shutting down EBAG9 allows the body to eradicate tumor cells earlier and more radically. As well as achieving longer-lasting therapeutic success, this could also create a real chance of cure,” says Rehm.

For patients with lymphoma, multiple myeloma or certain types of leukemia, treatment with CAR T cells is sometimes the last chance of overcoming the cancer. But even after treatment, many patients relapse because the tumor cells can outwit the CAR T cells by producing more of the protein EBAG9 – and by causing the T cells to produce more of it, too. In T cells, EBAG9 inhibits the release of cytotoxic enzymes, which slows the desired immune response.

However, the first-line therapy for blood cancer will remain chemotherapy combined with conventional antibody therapy, as many patients respond very well to this. “CAR therapy only comes into play if the cancer returns. It’s very expensive because it’s an individual cellular product for a single person,” says Dr Höpken. And a single treatment with that product can save a life.

The researchers will present their concept to the Paul Ehrlich Institute, Germany’s biologics approval agency, in November.

Thanks to their findings from animal models and the in vitro experiments using human cells, the team now knows that releasing the EBAG9 brake is highly effective and doesn’t cause any more side effects than conventional CAR T therapy. “We now need bold clinicians and a partner for financing the clinical studies,” says Dr Rehm. “If everything goes well, the therapy using EBAG9-silenced CAR T cells could be available to patients in as little as two years’ time.”