High dose chemotherapy is now a commonly used approach for treatment of hematologic and other cancers, but causes severe myelosuppression requiring progenitor cell infusions. Purging cancer cells from infusions, while maintaining progenitor cells, is an important goal in optimizing the curative potential of this technology. Current purging techniques have limited efficiency and demand intensive time, technology and cost. We have demonstrated a new technology that selectively kills larger cells (including tumor cells) while preserving or enriching hematopoietic progenitor cells, and does so rapidly, profoundly and inexpensively. In phase II, we will apply this technology to a relevant hematologic cancer model (multiple myeloma). Process parameters will be refined to achieve complete tumor purging and progenitor cell preservation/enrichment from tumor-seeded blood or cord blood cells. Sensitive and accurate cell enumeration will be achieved through flow cytometry, tumor regrowth assays, real-time PCR, progenitor cell quieseence/pluripotency assays, and in vivo hematopoietic reconstitution and malignancy assessment in NOD/SCIDt,B2m about mice. We will then apply refined parameters and assessment techniques to clinical volumes of bone marrow cells from myeloma patients, utilizing an optimized, clinical-scale flowing process apparatus. We anticipate the Phase III effort will involve Phase II clinical trials supported by a major biomedical partner.
We expect PEF cell-size specific inactivation technology to be an effective transplant tissue purging strategy for post-intensive-therapy patient support. With the propose refinements and assessments, it should provide an approach for rapid, cost-effective, high purity isolation of stem cells from progenitor cell preparations, which will open research, clinical, gene therapy and stem cell banking markets. Our market analysis indicates that the total revenues for this technology may eventually reach $100 million per year.
| Craiu, Abie; Saito, Yoriko; Limon, Ana et al. (2005) Flowing cells through pulsed electric fields efficiently purges stem cell preparations of contaminating myeloma cells while preserving stem cell function. Blood 105:2235-8 |
