The University of Arizona Cancer Center performed experiments indicating that a triple-combination therapy might significantly boost the immune system’s ability to fight cancer and improve patient survival. Collaborating with researchers at the Medical University of South Carolina, the team published its results online in “Clinical Cancer Research” in October 2018.
This is good news, but its use will be slow in implementation, says Andrew S. Kraft, M.D., director of the UA Cancer Center.
The group focused on a protein called PIM kinase, which normally is integral for cell growth, but can go awry to cause cancer. Their experiments suggested that when combined with two types of immunotherapy treatments, a drug that “blocks” PIM kinase could help extend immune memory, enabling a longer-lasting immune response.
“The focus on PIM came out of my laboratory,” says Kraft. “PIM kinase is an important target in cancer. This collaborative work shows that inhibiting this enzyme can greatly enhance immunotherapy and impact cancer.”
T cells, the “foot soldiers” of the immune system, eliminate threats such as viruses and bacteria. Theoretically, they should be able to seek and destroy cancer, but often they need help recognizing tumors as “foreign.” In recent years, immunotherapy has been used to “train” patients’ T cells to recognize cancer and mount an aggressive immune response.
Adoptive T cell therapy (ACT) is a type of immunotherapy that involves infusing patients with T cells with strong anti-cancer properties. These “supercharged” T cells, however, can die out before the disease clears, leading to relapse. By combining ACT with a PIM inhibitor and another type of immunotherapy called a checkpoint inhibitor, the UA and MUSC teams were able to extend that immune response in lab experiments, as the inhibitors prolong the life of adoptive T cells.
Their experiments pitted this triple-combination therapy against melanoma, the sixth-most common cancer in Arizona, according to the Arizona Department of Health Services — but their results could have implications for other cancer types as well. The hope is that better drug combinations will expand treatment options for patients and extend their survival.
“PIM inhibitors have been developed by multiple pharmaceutical companies,” Kraft says. “They need to go into trials in a more diverse group of tumor types to make an impact on cancer treatment and patients’ lives.”
Kraft further explained to the AJP that it would be a matter of time before the therapy gets to patients, although ACT already is in use in humans. The three components must be trialed and found safe and effective individually before they can be combined. “Then it will take time and convincing to get the pharmaceutical companies to do it,” Kraft adds.
In addressing Israel’s Accelerated Evolution Biotechnologies Ltd. recent claim of discovering a complete cure for cancer Kraft says, “Everyone is trying new and novel things. We’d all like to cure cancer.” While the AEBi system uses peptides to deliver toxins to kill cancer cells, Kraft notes that there are Federal Drug Administration-approved agents that have antibodies linked to toxins that already are in use in some patients. “It’s hard to tell where they are in trials” with the Israeli approach.
An accomplished cancer researcher and drug developer, Kraft left MUSC in 2014 to lead the UA Cancer Center. He is the Sydney E. Salmon endowed chair, associate vice president for oncology programs for the UA Health Sciences, and professor of medicine and senior associate dean for translational research at the UA College of Medicine — Tucson. Between college and medical school, Kraft attended Weizmann Institute of Science in Rehovot, Israel, spending three months in the biochemistry department.
“Everything is a building experience. We build our expertise. This experience helped me build mine,” he says.
The UA Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center with headquarters in Arizona, with more than a dozen research and education offices throughout the state, and more than 300 physicians and scientists working together to prevent and cure cancer. For more information, visit www.uacc.arizona.edu.
AJP Assistant Editor Debe Campbell contributed to this report.