Lung cancer has long been considered a disease that might benefit from the dose escalation of radio/
chemotherapy afforded by a stem cell transplant. However, the clinical experience with high-dose
chemotherapy and autologous
bone marrow transplantation in
lung cancer has been disappointing, with most trials showing little or no improvement in long-term survival. Unfortunately,
lung cancer has a tendency to metastasize to the bone marrow, and
lung cancer cells are known to circulate in the peripheral blood. Therefore, there is concern that autologous stem cell grafts from
lung cancer patients may reinoculate recipients with live
tumor cells. Photochemical purging of stem cell grafts with
Merocyanine 540 (MC540) is highly effective against a wide range of
leukemia and
lymphoma cells and is well tolerated by normal hematopoietic stem and progenitor cells. Most solid
tumor cells (including
lung cancer cells), however, are only moderately sensitive or refractory to MC540-mediated
photodynamic therapy (
PDT). We report here that postirradiation
hyperthermia (< or = 42 degrees C, 3 h) potentiates the MC540-mediated photoinactivation of both wild-type (H69) and
cisplatin-resistant mutant (H69/CDDP)
small cell lung cancer cells by several orders of magnitude, while only minimally enhancing the depletion of normal human granulocyte/macrophage progenitor cells. Our data suggest that postirradiation
hyperthermia provides a simple and effective means of extending the utility of MC540-PDT to the purging of stem cell grafts contaminated with
lung cancer and possibly other solid
tumor cells.