High dose chemotherapy is now a commonly used approach for cancer, but causes severe myelosuppression requiring autologous progenitor cell (PC) infusions. Purging cancer cells from these infusions is now recognized as an important goal in minimizing tumor relapse. Several techniques yield two-five log tumor cell reductions, but often with PC toxicity, intensive time/technology requirements, or high cost. We have demonstrated that pulsed electric fields (PEFs) selectively kill larger (epithelial tumor) cells without detectable damage to smaller (normal hematopoietic progenitor) cells critical for immune system reconstitution. Thus, PEFs show great promise as an effective PC purging strategy. In Phase I, using flow cytometry and PCR, we will optimize this strategy with respect to one of five key parameters and demonstrate its capability for six log tumor cell reduction while preserving the viability of PCs. Phase II will optimize all PEF parameters and demonstrate purged PC function via a novel NOD/SCID animal model. We anticipate demonstrating safety and feasibility in Phase I clinical trials involving intensive therapy breast cancer patients using an instrument such as the US Army Breast Cancer Research Program. We also anticipate the Phase III SBIR effort will involve Phase II clinical trials supported by a major biomedical partner.
We expect the PEF cell-size specific inactivation technology to be an effective transplant tissue purging strategy for post-intensive-therapy patient support. With further refinement, it should offer an approach for rapid, cost effective, high purity isolation of stem cells from progenitor cell preparations, which will open research, clinical, military, and stem cell banking markets. Our market analysis indicates that the total revenues for this technology may eventually reach $100 million per year.
