Enhanced CpG Activated Macrophage Killing of 3-Bromopyruvate Pre-treated 4T1 Breast Cancer Cells

A common feature of breast cancer cells is the
evasion of singular treatments by using the Warburg
Effect, a process of metabolic ATP production
through rapid anaerobic glycolysis. Cancer research
has transitioned to an investigation of combination
therapies to combat cancer. In our study, we seek
to metabolically inhibit cancer cells before application
of immunogenic killing. The Warburg Effect
was targeted with 3-Bromopyruvate (3-BP), which
blocks Glyceraldehyde 3-Phosphate Dehydrogenase
(GAPDH) production. Treatment with 3-BP yielded
up to 86.5% cancer cell death. Glycolytic inhibition
renders cancer cells metabolically stressed, which
may enable an effective immune response. Our
hypothesis was that CpG activated macrophage
will possess tumoricidal potential to target metabolically
stressed cancer cells. Macrophages and
CpG cultivation alone yielded a significant immune
response. We sought to find a synergistic effect of
3-BP induced killing susceptibility with CpG activated macrophages may lead to an effective method of
combination therapy.