SLC13A3 is revealed here, for the first time based on our evaluation, as a transporter for itaconate in tumor cells which plays a role in promoting tumor ferroptosis resistance, thereby weakening tumor immunity and immune checkpoint blockade (ICB). World renowned immuno-oncology leaders from UTHealth and University of Michigan (UMich) have identified a panel of monoclonal antibodies with therapeutic and diagnostic potential targeting SLC13A3 immune modulation axis, potentially pioneering the novel class of immunotherapeutics of specific antibodies in clinical trials.
Despite the remarkable clinical efficacy achieved by current cancer immunotherapy, most patients remain unresponsive to such treatments while facing high risks of therapeutic resistance to ICB. In addition, there exists a significant knowledge gap on how tumor cells utilize the immunosuppressive oncometabolites existing in abundance in the tumor microenvironment (TME) to evade anti-tumor functionalities delivered by immunotherapy. Therefore, understanding the underlying resistance mechanisms and further identifying new therapeutic targets are key to improving immune-oncological treatment outcomes.
UTHealth and UMich researchers discovered a method through which inhibitors of SLC13A3 block its tumor-protecting functions, identifying SLC13A3 as a promising target for immunotherapeutic treatments of cancer. Researchers revealed the previously unreported role of SLC13A3 as a transporter gene for itaconate in tumor cells, promoting ferroptosis resistance and thereby lowering the efficacy of such treatments. A panel of monoclonal antibodies was identified as potential immunotherapeutic candidates targeting SLC13A3 immune modulation axis.
The novel SLC13A3 monoclonal antibody can be used in the diagnosis and treatment of various types of cancer and auto-immune disease. No specific antibody has been in clinical trials, based on our evaluation, and there exists a great demand for cancer immunotherapies with improved clinical outcomes. Therefore, anti-SLC13A3 antibodies exhibit promising potential as novel immunotherapeutics, thanks to their activities against this transporter gene’s cancer-protecting itaconate absorption.
PCT/US2025/046702 filed.
Available for Licensing.
Lin, Heng, et al. "Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance." Cancer Cell (2024).
Zhiqiang An, PhD
Vice President of Drug Discovery at UTHealth Houston
Dr. An is a world leader in the development of antibody-based biologicals to treat cancers, with multiple drug candidates currently in clinical trials.
Weiping Zou, PhD
Director of Center of Excellence for Cancer Immunology and Immunotherapy at University of Michigan
Dr. Zou is an internationally recognized leader in human tumor immunology and immunotherapy, amassing over 74,000 citations.