These findings demonstrate that MSLN is a viable target for CAR T therapy in AML and that inhibiting MSLN shedding is a promising approach to improve CAR T efficacy.
The MTD for single-agent LMB-100 was found to be 140 µg/kg given on a schedule of every other day for 3 doses every 3 weeks. Although less immunogenic than the first-generation antimesothelin immunotoxin SS1P, the majority of patients developed antidrug antibodies after 2 cycles, indicating that LMB-100 has limited antitumor efficacy as a single agent. Phase 2 studies of LMB-100 plus pembrolizumab currently are ongoing for patients with mesothelioma and lung cancer.
This has led to multiple clinical trials, testing the safety and efficacy of the clinical leads SS1P and LMB-100. This review summarizes existing pre-clinical and clinical data on MSLN-targeted iTox's. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents.