Emerging Approaches in Immunotherapy

Juhi Kunde, MA, LUNGevity Science Writer

Immunotherapy, the treatment approach that harnesses the body’s natural immune system to fight disease, has become an important option for patients with advanced-stage lung cancer in just a few years. Depending on certain conditions, including that the patient not have an EGFR or ALK genomic mutation, a patient’s first-line of treatment may include immunotherapy, often in combination with chemotherapy. However, while immunotherapy can have long-term benefits for some patients, many patients do not respond to it.

“Researchers are working to improve patient outcomes by improving current immunotherapy protocols and developing new ones,” says Edward Garon, MD, professor of Medicine at the Jonsson Comprehensive Cancer Center at UCLA and a member of LUNGevity’s Scientific Advisory Board. “In general, the field of immunotherapy has created a lot of interest and opened up a lot of possibilities for researchers.” 

With the success of immunotherapy in treating lung cancer, we have seen an increase in creative and innovative treatment approaches that strive to leverage the immune system to fight lung cancer.

Checkpoint Inhibitors

The immunotherapies currently used for treating lung cancer are part of a class of drugs known as checkpoint inhibitors. These drugs block an important interaction between PD-L1 (found on tumor cells) and PD1 proteins (found on T-cells of the immune system). When these proteins interact, it serves as a halt signal for the T-cells and stops them from attacking the tumor. Our current catalog of immunotherapy treatments targets this protein interaction to take the brakes off the immune system and allow the immune system to fight disease more effectively.

However, many other protein interactions are involved in regulating the immune system, and researchers are studying them to find new ways to leverage the immune system when fighting lung cancer.

Cell Therapy

The National Cancer Institute has been interested in developing immune cell therapies for many years. Researchers are taking lymphocytes (a type of white blood cell) from patients' blood and then growing and modifying the lymphocytes in the lab to target the tumor. These modified cells are then returned to the patient. Researchers are hoping to bolster the immune system’s ability to respond to the tumor. Clinical trials are already underway to determine if this approach could benefit patients with recurrent advanced non-small cell lung cancer. 

Research into one type of cancer treatment often influences the treatment of other cancers. In the case of immunotherapy, blood cancers have seen good results with a type of treatment called CAR-T cell therapy. First, T-cells (a specific type of lymphocyte) are harvested from the patient. Then, the T-cells are modified in a laboratory to include a CAR (chimeric antigen receptor) protein, to enable the T-cells to bind to the cancer cells and kill them. Finally, millions of these CAR T-cells are grown in the laboratory and then infused back into the patient.

“This process can be very effective in killing a high percentage of a specific type of cell in the blood, but it is more complicated to do in the lungs because the lungs still need to function to appropriately oxygenate the blood,” explains Dr. Garon. “Researchers are making sophisticated adjustments to try to adapt this approach for lung cancer treatment.”

Vaccines

Early phase clinical trials are also helping researchers develop a vaccine for lung cancer treatment. Unlike common vaccinations, such as the flu shot, these vaccinations would be given to treat lung cancer, not to prevent it.

“This creates a unique type of challenge that researchers have been grappling with,” explains Dr. Garon. “We are finding ways to ‘re-teach’ the immune system that the cancer cells shouldn’t be there.”

Researchers are working on vaccines that have been loaded with the most common lung-cancer-related antigens to alert the immune system to disease. Several of these treatment vaccines are already being studied in clinical trials.

“This is an exciting time for immunotherapy research,” notes Dr. Garon. “There is a lot of potential for new discoveries and significant improvements for patients. With nonprofits like LUNGevity helping to raise awareness and funds for lung cancer research, I am hopeful for the future.”

 

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Juhi KundeJuhi Kunde, MA, is a science writer for LUNGevity.

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