The Long Run with Luke Timmerman Ep188: Art Krieg on Innate Immune System Activators for Cancer
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Oct 28, 2025 Art Krieg, a pioneering physician-scientist and CEO of Zola Therapeutics, discusses groundbreaking work in cancer immunotherapy. He shares how his early medical experiences shaped his interest in immunology and led to the discovery of immune-stimulatory CpG DNA. Art recounts his journey through clinical trials, exploring the balance between successes and setbacks. He explains Zola's innovative approach using synthetic retroviral particles to activate immune responses, all while emphasizing the importance of learning from veterinary studies to inform human applications.
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Serendipitous Discovery Of CpG DNA
- Art recounts discovering control oligonucleotides that unexpectedly drove strong B-cell proliferation in his University of Iowa lab.
- That observation led him to identify the CpG motif and publish the 1995 Nature paper that launched Coley Pharmaceuticals.
Why Unmethylated CpG Activates Immunity
- Art realized unmethylated CpG dinucleotides in bacterial DNA drive immune stimulation while methylation abrogates it.
- That mechanistic insight explained why bacterial DNA activates immunity and formed the basis for immunotherapy and adjuvant work.
Mixed Clinical Outcomes At Coley
- At Coley Pharmaceuticals Art ran clinical trials across vaccines, infectious disease, allergy, and cancer with mixed outcomes.
- Two phase III cancer trials failed despite early promise, which he called gut-wrenching and part of biotech realities.