DALLASUniversity of Texas M.D. Anderson researchers plan to test whether removal of residual breast cancer cells from stem cell transplant grafts will improve the long term success of such transplants for patients with late-stage metastatic breast cancer.
Such patients currently have quick relapse of the cancer after high-dose chemotherapy with stem cell support. However, none of the transplant studies reported to date used grafts that were fully devoid of tumor cells, said Frank Marini, PhD, of the Section of Molecular Hematology and Therapy, Department of Blood/Marrow Transplant.
We have created a novel breast cancer purging technique by combining two independent eradication strategies, said Dr. Marini, who presented his work at the Susan G. Komen Foundation National Grants Conference (Reaching for the Cure: The Next Step).
At M.D. Anderson, he said, patients are transplanted only on clinical trials. It appears promising in patients with local breast cancer (stages II and III) with high-risk features and in patients with chemotherapy-responsive metastatic disease, he said. There were 100 breast cancer transplants in 1998 at M.D. Anderson, and 61 such transplants in 1999.
The eradication strategy includes specific enrichment of stem cell progenitor CD34+ cells in the graft by magnetic antibody separation purification via the ClinicMACS device (Miltenyi Biotec/Amcell). This is followed by infection of the enriched stem cells by a recombinant adenoviral vector that preferentially infects contaminating breast cancer cells but not hematopoietic cells (see Figure).
Using these two techniques together, we can reduce the number of contaminating breast cancer cells by 5 to 7 logs, thereby providing a graft free of tumor, Dr. Marini said.
The magnetic antibody separation device uses antibodies that bind to stem cells and selects them in a magnetic column.
For adenoviral virus purging, the researchers generated a recombinant adenovirus carrying the bifunctional protein GAL-TEK (known as adGAL-TEK). Cells infected with adGAL-TEK are forced to commit suicide by the addition of the prodrug ganciclovir(Drug information on ganciclovir) [Gemzar], Dr. Marini said.
A clinical trial is planned using the combined enrichment/purging technique in 10 to 12 women with late-stage breast cancer and histologic evidence of disease in blood and bone marrow. The protocol is currently under review by the institutions IRB.
We will assess whether our genetic purging strategy is safe and effective for removing contamination and whether it has any impact on the quality of the stem cell graft, Dr. Marini concluded. His colleagues in the study are Drs. V. Snell, R. Champlin, and M. Andreeff, in collaboration with S. Eva Singletary, MD, Surgical Breast Oncology, and Gabriel Hortobagyi, MD, Breast Oncology.