Small Molecule Targets CD38 Enzyme to Fight Cancer

Researchers at the Medical University of South Carolina (MUSC) Hollings Cancer Center developed small molecules that could be used to stimulate immune cells to fight cancer. The team believes this could be one of the first times small molecules have been used in this way, with the potential to be used as adjuvant therapy for various cancers.

The compounds work by inhibiting the enzyme activity of CD38, which can be found on immune cells, including natural killer immune cells. While previous monoclonal antibodies bind to cancer cells to destroy them, this new small molecule targets the dual function of CD38 to make adenosine, which in high levels suppresses the body’s immune response.

In a paper published in RSC Chemical Science, the team describes how they screened an open-access library of compounds to look for small molecules that could target CD38’s enzyme activity. Once they identified a candidate, they refined the structure to create a new compound that targets CD38 and stimulates the proliferation of natural killer cells. These cells can then attack and kill cancer cells. The team tested this compound on neuroblastoma cells and found that it stimulated the natural killer cells to multiply, making them more effective at attacking and killing cancerous cells.

While the researchers believe this new small molecule could be used to treat neuroblastoma, there is hope it could also be used for other cancers. PD1 blockade has been successful in patients who respond well, but only a small subset of patients responds. With a small molecule adjuvant agent, the scope of patients who respond to therapy may be improved. Additionally, there is hope that this new small molecule could help reduce antibiotic resistance, which is widespread in high-risk neuroblastoma patients, ultimately making them ineffective.

The use of small molecules in cancer treatment is an area of growing interest, as they are much more likely to enter cells due to their low molecular mass. Small molecules are also structurally much simpler than monoclonal antibodies. The team hopes to make further refinements to the compound to make it more effective and easier to manufacture. They will also continue to search for other compounds to target CD38.

This early work is promising, and the researchers caution that drug discovery is a long road. While the team is hopeful that these early steps will culminate in a new therapy for neuroblastoma and other cancers, they stress that it is still very early in the process, and additional work is needed to further validate their findings.