High-dose
chemotherapy combined with autologous stem cell support has improved response rates in high-risk and metastatic
breast cancer, but has failed to improve long-term survival.
Breast cancer has a tendency to metastasize to the bone marrow, and live
tumor cells are known to circulate in the peripheral blood of
breast cancer patients. Sensitive immunohistochemical, culture-based, and
reverse transcriptase polymerase chain reaction (RT-PCR)-based methods have shown that about 50% of histologically normal stem cell grafts from
breast cancer patients are contaminated with occult
tumor cells, which may cause or contribute to
tumor recurrences.
Merocyanine 540 (MC540)-mediated
photodynamic therapy (
PDT) inactivates a wide range of
leukemia and
lymphoma cells and is well tolerated by normal hematopoietic stem and progenitor cells. Unfortunately, most solid
tumor cells (including
breast cancer cells) are only moderately sensitive or refractory to MC540-PDT. We report here that if MC540-PDT is followed by a 1-h incubation with the alkyl-
lysophospholipid,
Edelfosine (ET-18-OCH(3)), the depletion of murine and human
breast cancer cells is greatly enhanced whereas the recovery of normal hematopoietic stem and progenitor cells is only minimally degraded. When used under conditions that reduce CD34-positive human bone marrow cells only 5.1-fold, and murine and human granulocyte/macrophage progenitors 6.8- and 3-fold, respectively, combination purging with MC540-PDT and
Edelfosine depletes murine (Mm5MT) and human (MDA-MB-435S)
breast cancer cells >17,000- and >125,000-fold, respectively. These data suggest that combination purging with MC540-PDT and
Edelfosine may offer a simple, safe and effective method for the ex vivo purging of autologous stem cell grafts from
breast cancer patients.