Building an arsenal to fight cancer

Dr. Dhaval Shah has spent the past three years searching for the Holy Grail of medicine: a cure for cancer. Shah, an assistant professor in the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, leads cutting-edge research focused on protein therapeutics and the engineering of proteins for medical use.

While he hasn’t found cancer’s cure, Shah has made progress in the way the disease is treated. His efforts have helped advance development of antibody-drug conjugates (ADC), a novel molecule that can target cancer cells directly, eliminating the toxic side effects of traditional chemotherapy.

These antibodies act as a Trojan horse, targeting receptors specific to cancer cells. When the ADCs reach the tumor, the molecules release the drugs hidden inside, which are then free to break the DNA within the cancer cells. But the drugs are only released if the ADCs reach their target, which prevents the chemotherapy treatment from harming healthy cells.

Shah’s study of ADCs caught the attention of Boston-based cancer drug developer Oncolinx. In the early stages of the startup, its founders Sourav Sinha and Riley Ennis reached out to Shah for guidance on merging ADCs with cancer medication. A mutual interest in protein therapeutics led Shah to eventually join the company as a scientific adviser.

“When you see someone doing the same science as yourself, you want to help them out,” says Shah. “Talking to people about science is what makes you a good scientist. The more I talk to like-minded people, the better my science becomes.”

The concept of targeted cancer treatment has existed for more than decade, but the technology to make such a drug was largely developed within the past five years, Shah says. There are now three ADCs approved for use, while another 50 are undergoing clinical trials.

Dr. Joseph Balthasar, professor and associate dean for research in the School of Pharmacy and Pharmaceutical Sciences, is also taking aim at cancer through research that will test new strategies for improving the delivery of potent toxins to cancer cells. The study “Catch and Release Immunotoxins: CAR-Bombs for Cancer,” led by Balthasar, received a five-year $1.8 million grant from the National Cancer Institute to support research that aims to use an untested method of delivering antibodies to target colon cancer cells that, if effective, could be applied to nearly any type of cancer.

“The strategy that we are pursuing is a ‘platform approach’ that may be applied to many different types of cancer,” says Balthasar, also director of the UB Center for Protein Therapeutics. “If our work is successful, we may be able to move forward to develop a panel of treatments, providing increased safety and efficacy for many cancer patients.”

Although advances have been made in the treatment of cancer with surgery, radiation and chemotherapy, there is a critical need to develop novel approaches with promise for improved selectivity, potency and efficacy, Balthasar said.

He will test a new treatment strategy that employs “catchand- release” antibodies that are bound to powerful toxins
and cell-penetrating peptides. These molecules target and bind to cancer cells, allowing for the efficient release of toxins into the cell’s cytoplasm—the fluid that fills a cell.

Preliminary data gathered to access the binding, toxicity and pharmacokinetics—how the body affects a drug—of the antibody support the feasibility of the method as a viable form of treatment, Balthasar said.