Track 1 (Patient-Centered Care) of Day 3 of the Precision Medicine World Conference (PMWC) 2018 began with a presentation by Ron Levy (photo), MD, Professor and Chief, Division of Oncology, Stanford University School of Medicine. Over a decade ago, Dr. Levy developed the first FDA-approved antibody for the treatment of cancer, rituximab, which is now used for every lymphoma patient, either as a standalone treatment on in combination with other therapies. Dr. Levy’s talk on this day was titled “A Better Way to Trigger the Immune Response Against Cancer.” Dr. Levy outlined a new combination immunotherapy approach that is described in a January 31, 2018 Science Translational Medicine article (http://stm.sciencemag.org/content/10/426/eaan4488). In a mouse model, Dr. Levy’s group showed that intratumor injection of the combination of unmethylated CG-enriched oligodeoxynucleotide (CpG), a Toll-like receptor 9 ligand (TLR9), and anti-OX40 antibody led to shrinkage of distant tumors and long-term survival of the animals, even in a stringent spontaneous tumor model. Low doses of CpG injected into the tumor induce the expression of OX40 on CD4+ T-cells in the microenvironment of the tumor. An agonistic anti-OX40 antibody can then trigger a T-cell immune response that is specific to the antigens of the originally injected tumor. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. In mice, the combination of CpG, TLR9, and anti-OX40 was shown to cure multiple types of cancer and to prevent spontaneous genetically driven cancers. Dr. Levy noted that one of the most spectacular results was seen in a model of spontaneous breast cancer where the combination treatment eliminated the cancer from all ten mammary glands in a very short time. Dr.
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