UB receives $2.1 million grant to prevent toxic side effects of leukemia treatment

BUFFALO, N.Y. – The University at Buffalo has received a five-year, $2.1 million grant from the National Cancer Institute to advance the safety and effectiveness of targeted drugs that treat acute myeloid leukemia – a cancer of the blood and bone marrow.

The research is co-led by Joseph Balthasar, PhD, David and Jane Chu Endowed Chair in Drug Discovery and Development in the UB School of Pharmacy and Pharmaceutical Sciences. The project aims to develop antibody-drug conjugates (ADC) – a class of drugs that target cancer cells – as well as payload-binding selectivity enhancers (PBSE), a class of drugs created in Balthasar’s lab that may help prevent anti-cancer drugs from harming healthy cells.

The ADCs that will be developed, which include bispecific ADCs that are expected to demonstrate increased selectivity for cancer cells by binding to them at multiple sites, deliver payload molecules that kill cancer cells efficiently. Unfortunately, healthy cells that are exposed to the payload molecules are killed nearly as efficiently as cancer cells, leading to toxicity. 

Balthasar’s PBSEs bind to payload molecules in blood, decreasing the delivery of the payload to healthy cells. Treatments that combine PBSEs with ADCs may enable effective anti-cancer activity while reducing unwanted toxicity, says Balthasar.

“Our PBSE drugs enable safe administration of high doses of ADCs, potentially allowing greatly improved therapy for many types of cancer,” says Balthasar, also director of the UB Center for Protein Therapeutics. 

Dhaval Shah, PhD, associate professor in the UB School of Pharmacy and Pharmaceutical Sciences, is also a principal investigator. Key researchers in the Balthasar Lab include Brandon Bordeau, PhD, research assistant professor, and postdoctoral fellow Toan Duc Nguyen, both in the UB School of Pharmacy and Pharmaceutical Sciences. 

The ADCs developed by the team will target three surface proteins overexpressed in acute myeloid leukemia. The PBSEs will be designed to sweep up ADC payload molecules that miss their target, helping to prevent collateral damage to healthy cells during treatment.

Using both pharmacokinetic and pharmacodynamic modeling and animal models, the researchers will also compare the effectiveness of ADCs that target one protein overexpressed in acute myeloid leukemia with that of ADCs that target multiple sites. Each drug will be tested with and without co-treatment of PBSEs. 

The PBSE drugs will be licensed from UB and developed through the startup Abceutics Inc. Founded by Balthasar, Bordeau, Nguyen and Larry Wienkers, PhD; the company has received funding from the National Institutes of Health and the Buffalo Innovation Accelerator Fund, and operates from incubator space in UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.