Research Aims to Outsmart Cancer by Reprogramming Immune System Cells

Ashish Kulkarni, assistant professor of chemical engineering at the University of Massachusetts Amherst, has been awarded a four-year, $792,000 grant from the American Cancer Society to advance his interdisciplinary lab’s promising cancer immunotherapy research. 

Building on the groundbreaking discoveries from an earlier studyinvolving melanoma and breast cancer in animal models, the new preclinical research focuses on urothelial bladder cancer, which has a high recurrence rate and has seen limited treatment breakthroughs in recent decades.

Current immunotherapy drugs for bladder cancer are effective only for a subset of patients, Kulkarni explains, because of the way the cancer suppresses the immune system. “Despite the standard of care, a lot of patients relapse,” he says.

The new immunotherapy strategy being developed addresses that challenge and has the potential to revolutionize bladder cancer treatment, Kulkarni says.

Cancer has a way of turning off the body’s immune system response so that macrophage cells that normally would attack the disease are not only rendered powerless but recruited to help the malignant tumor grow. “We want to reverse that,” Kulkarni says.

His team designs so-called self-assembled supramolecular nanoparticles, which are capable of simultaneously targeting the immune suppressor cells in tumors and reactivating the immune cells capable of eating the tumor. These supramolecules are designed from lipids, some of the body’s own building blocks, and have been found to be nontoxic, versatile and efficient in the delivery of drugs and other biomedical materials.

“This research brings together the latest advances in cancer immunotherapy with novel biomaterials to engineer a nanotherapeutic platform to activate innate and adaptive immunity,” Kulkarni says. “This novel combination therapy increases the impact and could result in a dramatic increase in survival in bladder cancer while minimizing the side effects of the therapy.”

His lab’s previous research with breast cancer and melanoma showed that the designer supramolecule was capable of repolarizing macrophage cells to inhibit tumor growth and metastasis, significantly improving survival in breast cancer and melanoma mice models. 

The new research seeks to determine the optimal dosage and test the nanotherapy’s safety and effectiveness in bladder cancer, again using mouse models. Kulkarni says the next step would be testing the immunotherapy regimen on people with cancer.

“We are hoping to have something that can translate into clinical trials in the future,” he says.