Clinical-stage human anti-transferrin receptor antibodies suppress colorectal cancer metastasis

Advanced colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with distant metastasis and therapeutic resistance representing critical clinical hurdles. 1 Transferrin receptor (TFRC), a key iron transporter that is frequently overexpressed in tumors, plays a vital role in tumor progression and is correlated with poor prognosis. 2 While TFRC inhibition has been shown to suppress growth in various cancers, 3 its therapeutic effect on the CRC metastatic cascade remains unexplored. While the safety of PPMX-T003 (a clinical-stage, fully human anti-TFRC monoclonal antibody) has been confirmed in phase 1 trials for hematological conditions and a phase 1/2 trial is currently ongoing for aggressive natural killer-cell leukemia, 4 , 5 its efficacy against solid tumors remains unknown. To our knowledge, this is the first study to evaluate the efficacy of PPMX-T003 against CRC, providing novel preclinical evidence that direct TFRC inhibition effectively suppresses both primary tumor growth and metastatic spread.