Finding a treatment that is effective for a large number of mesothelioma and lung cancer patients has been extremely challenging for researchers. Although chemotherapy is the primary course of treatment for these patients, the resistance the cancer inevitably builds up to the therapy can mean a dead end for their care. Now, researchers looking for a more inclusive treatment may have found a way for tumors that no longer respond to chemotherapy to respond to immunotherapy treatment.
Researchers from Massachusetts General Hospital have found a way to sensitize previously resistant tumors to immunotherapy checkpoint blockade. Immune checkpoints are likened to “immunological brakes” that allow tumors to escape detection by the immune system, and suppress cytotoxic T cells (CTLs), or immune cells that kill cancer cells.
However, checkpoint inhibitors release those brakes and “may enhance the anti-tumor T-cell response,” thus allowing the patients’ natural defense mechanisms to kick in and fight off mesothelioma and other cancers, according to Dendreon Corporation, a Seattle-based biotechnology company with a mission to target cancer with an immunotherapy focus.
“Immune checkpoint blockade has revolutionized cancer therapy because it can durably control tumor progression, even in patients who fail to respond to other treatments,” says Mikael Pittet, PhD, of the MGH Center for Systems Biology, senior author of the study, in the press release. “But the drawback is that it only benefits a fraction of patients. We have found a way to make unresponsive lung tumors sensitive to checkpoint blockade immunotherapy and achieve long-lasting control of tumor growth in these animal models.”
According to a Feb. 16 press release, the MGH researchers were able to amp up the immune system and control tumor growth as well. The team discovered that certain chemotherapy treatments induce CTLs. The researchers then forced CTLs into lung cancer tumors, in animal models, that had become resistant to chemotherapy to assess whether CTLs added to tumors would be effective cancer fighters.
The researchers found that after treating resistant lung cancer cells with a specific combination of chemotherapy found to induce CTLs, the cancer grew more slowly. When the immunotherapy blockade was added, the combination “durably controlled tumor growth in the lung cancer mouse models, which neither treatment was able to do alone.”
“Since the drugs shown to work in this study are all FDA-approved, the combination could be quickly tested in patients with lung cancer,” says Pittet. “We also plan to explore whether precision medicine approaches, which could identify drugs that best promote tumor infiltration by CTLs in a given patient, could extend the benefits of checkpoint blockade to even more patients.”
Lung cancer is the leading cancer killer for both men and women in the US, with approximately 160,000 Americans dying from the disease each year. Nearly 3,000 Americans succumb to mesothelioma, an asbestos-caused cancer, each year.
Mesothelioma and lung cancer are both notoriously aggressive and difficult to treat. This research shows that by combining the primary treatment protocol, chemotherapy, with immunotherapy, patients may have new options.
The study can be found in the Feb. 16 issue of the journal Immunity.