Researchers Use STING Agonists to Reverse Resistance to Rituximab in Lymphoma Patients

According to a recent study, adding a stimulator of interferon genes (STING) agonist to rituximab for lymphoma can help provoke an immune response to the monoclonal antibody in patients who had shown resistance.

The study, published in Cancer Research, explains that rituximab stimulates macrophages to attack the lymphoma cells, but some patients’ tumors suppress the efficacy of these macrophages by inhibiting Fcg receptors, thus rendering rituximab ineffective. The researchers experimented with several reagents, notably STING and toll-like receptor (TLR) agonists, to see if adding these to rituximab therapy could help provoke a tumor-fighting response in the cells.

In vitro, the STING and TLR agonists both triggered cytokine release, changed the expression of the Fcg receptors, and boosted the ability of rituximab to engulf the tumor cell. However, when tested in vivo on mice with lymphoma, only the STING agonists were consistently able to reverse the immune resistance and achieve these results. The researchers wrote that these agonists “provid[ed] strong adjuvant effects” to rituximab, which is a monoclonal antibody that targets and binds to the protein CD20.

“We’ve shown that STING agonists can help to 'rev up' immune cells and reverse attempts by the tumour cells to suppress them,” said senior author Stephen Beers, PhD, in a press release from his institution, the University of Southampton. “There are promising early signs that this approach could be used to improve treatment for people with lymphoma.”

The study also called adjuvants like STING agonists “appealing candidates” as they are able to reprogram macrophages and “curb tumor-mediated immunosuppression.” Beers noted that the STING agonists will next undergo laboratory testing and refinement “to make them as effective as possible at stimulating the immune system in lymphoma patients.”

As interest in harnessing the immune system to fight cancer grows, immuno-oncology has become a priority for the University of Southampton. Its Centre for Cancer Immunology, due to open next year, will be the first and only immuno-oncology research center in the United Kingdom. It intends to “bring world-leading cancer scientists together under one roof and enable interdisciplinary teams to expand clinical trials and develop lifesaving drugs.”

In the University’s press statement, Peter Johnson, MD, chief clinician of Cancer Research UK, suggested that STING agonists could potentially be investigated as one of these promising therapies.

“This exciting research suggests that using drugs to re-programme the cells around a cancer may make antibody treatments much more effective in the future, and we should be able to start testing this in the clinic very soon,” Johnson said.