About the Investigator:

Dr. Dahan studies the mechanisms that control the activity of both natural and therapeutic antibodies. He received his BSc and PhD degrees from the Technion, Israel Institute of Technology and carried out postdoctoral research at Rockefeller University in New York City. He is currently an Assistant Professor in the Department of Immunology at the Weizmann Institute of Science.

About the Research:

The immune response fights cancer, and considerable effort has been devoted to developing strategies that will stimulate immune cells to eliminate tumors from the body. Antibodies that stimulate the CD40 receptor on B cells were initially thought to herald the next generation of cancer immunotherapies. However, clinical trials were very disappointing, as toxicity occurred at high-antibody doses, and low doses had little effect.

The goal of this project is to optimize a new platform for CD40 antibodies that will bypass the dose-limiting toxicity of this type of immunotherapy. In their recent ICRF-funded study (a Research Career Development Award, funded 2018-2021), Dr. Dahan’s team engineered novel “bi-specific” antibodies that activate both CD40 and dendritic cells. These first-generation bi-specific antibodies provided proof of concept, as the therapeutic dose was considerably improved, compared to their parental antibody, but it was not yet suitable for clinical applications. Dr. Dahan now proposes to generate and characterize new versions of these antibodies in order to achieve a highly favorable therapeutic index. This research is expected to produce an optimized human antibody for cancer immunotherapy that will enable translation of this promising immune pathway targeting approach into clinical practice.