Researchers have revealed a new approach to cancer therapy that shows the potential to transform the commonly used chemotherapy drug gemcitabine into a drug that kills cancer cells in a specialized way, activating immune cells to fight cancer.
The findings, made in human and mouse cancer cells and laboratory mice, were published in the peer-reviewed journal Nature Communications on Monday.
The research team discovered that when they added the anti-inflammatory medication celecoxib (Celebrex) to gemcitabine chemotherapy, it converted gemcitabine from a non-immunogenic drug-unable to activate a patient’s own immune response-to an immunogenic drug, which triggered the immune response in the mice.
“The combination of drugs delivered a “one-two punch” of killing tumor cells and activating immune cells, said study author Keith Syson Chan from the Taipei Medical University in Taiwan.
“I believe that our study has significant clinical potential, as cancer immunotherapy continues to emerge as an important pillar for treating cancer patients,” Chan said.
This discovery, if confirmed in clinical trials, may potentially increase the percentage of patients who respond to cancer immunotherapy.
Certain chemotherapy drugs such as gemcitabine do kill cancer cells and release the “go” signal for an immune response. Scientists, therefore, have believed that those drugs are immunogenic. That is not entirely the case, though.
In a surprise discovery, they found that while gemcitabine does release the “go” signal, it also prompts the release of an inhibitory signal, or brake, that stops dendritic cells from activating cancer-killing T cells. If the brake is on, “the T cells don’t go anywhere,” Chan explained.
It is necessary, therefore, to find a balance between the “go” and “brake” signals to prompt an effective immune response.
The solution to that balance, the investigators discovered, is the anti-inflammatory drug celecoxib, which removed the brake so that only the “go” signal remained.
The dendritic and T cells then were better able to perform their immune responses. Gemcitabine was transformed into an immunogenic drug.
“Rather than focusing on stepping down harder on the gas pedal-releasing proteins that are “go” signals-we removed the impending brake pedal, allowing the dendritic cells to induce T cells to kill tumors.”
The researchers believe that the immune response will perform even better with an immunotherapy drug added to a gemcitabine and celecoxib treatment regimen.
