Summary Researchers at OHSU have discovered a novel combination therapy for triple negative breast cancer, which increases immune responses, causes tumor regression and improves survival in animal models.
Technology Overview Triple negative breast cancer (TNBC) represents one of the most aggressive forms of all breast cancer subtypes with a very high rate of recurrence. A recently approved immune checkpoint inhibitors (ICI) for TNBC patients increases median overall survival by ~7 months. However, median overall survival is still under two years even with the use of ICI and 50% of TNBC patients showed no improvement in response to ICI.
To search for better treatments to overcome this resistance to ICI, OHSU researchers used a macrophage and T cell co-culture drug-discovery assay to mimic macrophage dependent T cell suppression in cancer. This platform uncovered that commonly used pain-relieving COX2 medicines, including indomethacin, act as potent myelomonocytic reprogramming agents that also possess a significant synergy with anti PD-L1 to increase T cell expansion. Testing in animal models demonstrated that this combination therapy led to significant tumor regression and improved overall survival in animal models of TNBC. This effect appeared driven by CD8+ T cells, as the improvements were reversed when these cells were ablated. Importantly, the utility of this combination therapy could extend beyond TNBC to other solid tumors.
Publication Kumar S, et al. Uncovering therapeutic targets for macrophage-mediated T cell suppression and PD-L1 therapy sensitization. Cell Rep Med. 2024 Aug 15:101698. DOI: https://doi.org/10.1016/j.xcrm.2024.101698
Licensing Opportunity This technology is available for licensing and co-development.