New study aims to reduce unwanted toxicity in cancer therapy

Targeted cancer therapy.

By Kara Sweet

Published July 9, 2021

Antibody-drug conjugates (ADCs) have played a substantial role in cancer treatment in recent years. Antibody-targeting improves the delivery of anti-cancer toxins to cancer cells, and ADC therapy is considered as a major advance beyond traditional chemotherapy.

However, undesired delivery of toxins to healthy cells remains problematic, and ADCs often cause severe side effects by killing cells in healthy tissues.

Joseph Balthasar, BS '91 & PhD '96, David and Jane Chu Endowed Chair in Drug Discovery and Development and professor of pharmaceutical sciences, has received a new $1.8 million R01 grant from the National Cancer Institute (NCI) to develop an “inverse targeting” strategy to increase the safety and efficacy of anti-cancer ADCs.

Applying innovations of the past to state-of-the-art anti-cancer drugs

“Our inverse targeting strategy may be applied to all antibody-drug conjugates in current use and in current clinical development. ”
Joseph Balthasar, PhD, Professor of Pharmaceutical Sciences, Director of the Center for Protein Therapeutics, Executive Director of University Research Initiatives

“Inverse targeting” was introduced in the 1990s by Balthasar and his PhD advisor at the University at Buffalo, Ho-Leung Fung, PhD. In this method, anti-drug antibodies are employed to alter the pharmacokinetics of anticancer drugs, preventing distribution of the drugs to healthy tissues.

By blocking drug distribution to healthy tissues, inverse targeting decreases the undesired toxicity of cancer therapy, allowing higher drug doses to be administered safely, and enabling improved anti-cancer efficacy.

The new NCI project, titled “Enhancement of ADC selectivity by inverse targeting: Mechanistic studies and optimization,” applies the inverse targeting concept to optimize therapy with anti-cancer ADCs. Balthasar and his students have developed a new class of drugs, termed payload-binding selectivity enhancers (PBSEs), that decrease the toxicity of ADC therapy without negatively impacting efficacy.

 “The inverse targeting strategy may improve the safety and efficacy of all ten ADCs on the market, and the approach may be applied to more than 100 ADCs in current clinical development," Balthasar says.

Balthasar and his students recently submitted patent applications relating to their strategy, and they have launched a start-up company, Abceutics Inc., to pursue clinical development of new PBSEs developed in the Balthasar lab.

The new project adds to Balthasar’s current work, which includes support from two separate $1.8 million NCI R01 grants that evaluate new strategies to deliver protein toxins to the cytoplasm of targeted cancer cells (Catch and Release Immunotoxins: CAR-Bombs for cancer) and new strategies to increase antibody distribution in solid tumors (Pharmacokinetic strategies to increase monoclonal antibody uptake, distribution, and efficacy for treatment of solid tumors).

Pharmaceutical sciences team effort

Balthasar credits several members of his lab and collaborating scientists as key contributors. Dhaval Shah, PhD '10, associate professor of pharmaceutical sciences, and Marilyn Morris, PhD ’84, SUNY Distinguished Professor and chair of pharmaceutical sciences, have joined Balthasar as a co-investigators on the new NCI grant. Other key contributors include Dr. Bruce Molitoris, distinguished professor of medicine and physiology at Indiana University, Brandon Bordeau, PhD '20, postdoctoral associate, and graduate students Jue (Joy) Gong and Toan Duc Nguyen.

For over 130 years, the University at Buffalo School of Pharmacy and Pharmaceutical Sciences has continually been a leader in the education of pharmacists and pharmaceutical scientists, renowned for innovation in clinical practice and research. The school is accredited by the American Council of Pharmaceutical Education and is the No. 1 ranked school of pharmacy in New York State and No. 14 in the United States by U.S. News & World Report.

For more information about the UB School of Pharmacy and Pharmaceutical Sciences visit

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Kara Sweet
Assistant Director, Communications and Alumni Relations