Researchers at the University of California, Los Angeles (UCLA) have developed a new treatment method using a nanocapsule to deliver the enzyme lactate oxidase into solid tumors, improving anti-tumoral immune response and immune checkpoint inhibitor therapy efficacy.
Reporting in Science Translational Medicine, scientists are targeting lactate—a chemical produced by cancer cells that makes it difficult for the immune system to effectively fight the disease. According to the researchers, previous methods to reduce lactate levels using inhibitors have also had significant effects on the metabolism of healthy cells, prompting the search for a less-invasive new approach.
“Cancer immunotherapy has reshaped the landscape of cancer treatment,” said Jing Wen, assistant adjunct professor of microbiology, immunology, & molecular genetics at UCLA and senior author of the study. “However, not all patients with solid tumors respond well to immunotherapy, and the reason seems to be related to the way the cancer cells affect their surroundings.”
In order to deliver their drug directly into the tumor microenvironment without harming the surrounding healthy cells, the researchers packaged the lactate inhibitor enzyme lactate oxidase into tiny nanocapsules. Apart from reducing lactate levels around and within solid tumors, the enzyme also releases hydrogen peroxide in the tumor, helping recruit and activate immune cells.
“When lactate is reduced and hydrogen peroxide is released, it makes it easier for the immune system to work against the cancer,” said Zheng Cao, first author of the study and UCLA Samueli School of Engineering doctoral candidate in the department of chemical and biomolecular engineering.
The researchers tested their nanocapsule drug delivery system in mice with melanoma and triple-negative breast cancer, performing tumor growth measurements, survival curve analysis, RNA sequencing and immune cell population analysis. According to the scientists, reducing lactate and producing hydrogen peroxide encouraged immune cells to enter the tumor, increasing the number of relevant immune cells by two to five-fold.
“We found lactate oxidase nanocapsules helped prevent the immune system from being weakened and overcome the immune suppression caused by the tumor,” Cao said. “Moreover, this dual-action approach improved the success of a specific type of cancer immunotherapy treatment called immune checkpoint blockade and we believe it could be an effective strategy to help make cancer immunotherapy more effective.”
As a next step, the researchers will further explore the role of lactate oxidase nanocapsules in enhancing therapeutic effectiveness of chimeric antigen receptor (CAR) T-cell therapy for solid tumors.
