Expert Point of View: Cornelius J.M. Melief, MD, PhD




Conceivably, motolimod can affect certain leukocyte subsets, such as myeloid-derived suppressor cells, but also positively affect other leukocyte populations, such as macrophages, dendritic cells, and natural killer cells.
— Cornelius J.M. Melief, MD, PhD

Cornelius J.M. Melief, MD, PhD, Emeritus Professor at Leiden University Medical Center in the Netherlands and Chief Scientific Officer at ISA Pharmaceuticals, noted that toll-like receptors (TLRs) are useful in promoting immune activation in a variety of leukocytes and that the signaling pathways differ widely among them. But, in general, “All TLRs have immune-stimulating properties that can arouse the sleeping immune system and promote cancer therapies,” he noted.

With regard to motolimod plus chemotherapy/cetuximab (Erbitux), he said, immunopathologic analysis of the injection-site reaction would be interesting, especially to look for correlations with favorable outcomes. “Conceivably, motolimod can affect certain leukocyte subsets, such as myeloid-derived suppressor cells, but also positively affect other leukocyte populations, such as macrophages, dendritic cells, and natural killer cells,” he said. He suggested investigating some of these aspects using purified leukocyte subsets in vitro.

Dr. Melief also wondered if there might be strategies to enhance the proportion of patients who develop injection-site reactions, such as by changing the chemotherapy or adding immunomodulators.

Tanguy Lim-Seiwert, MD

Tanguy Lim-Seiwert, MD

Tanguy Lim-Seiwert, MD, of the University of Chicago, emphasized during the discussion period that, as a post hoc analysis, the results should be viewed with caution. “An alternative interpretation of the injection-site reaction may simply be that it’s a prognostic biomarker,” he offered. “Maybe we are simply identifying patients with a more immunocompetent state for whom motolimod may not have any effect. The problem is there were no injection-site reactions in the control arm. I’m not saying it’s not true, but we need caution.” ■

Disclosure: Dr. Melief reported no potential conflicts of interest.


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