A revolutionary therapy for intractable diseases including malignant tumors
First Department of Pathology, Regeneration Research Center for Intractable Diseases, Center for Cancer Therapy, Transplantation Center, Kansai Medical University, Kansai Medical
Donor lymphocyte infusion (DLI) has been proposed as a strategy for the treatment of not only hematopoietic malignancies but also malignant solid tumors. However, there has been no strategy either to discriminate between graft-versus host reaction (GvHR) and graft versus tumor reaction (GvTR) or to prevent and treat GvHD. We have recently developed a new bone marrow transplantation (BMT) method. This method includes a “Perfusion Method (PM)” for bone marrow cell (BMC) harvesting (Stem Cells 18: 453-456, 2000) and intra-bone marrow (IBM) injection of BMCs (“IBM-BMT”) (Blood 97: 3292-3299, 2001). “PM”, using the long bones instead of the iliac crests, allows us to prevent the GvHD that results from the contamination with T cells from the peripheral blood in cynomolgus monkeys. “IBM-BMT” allows us to efficiently recruit both donor hemopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), which results in a rapid recovery of both hemopoiesis and lymphopoiesis (including T cells). In addition, we have very recently found that IBM-BMT can be used to prevent and treat acute GvHD induced by DLI, since donor-derived stromal cells (including MSCs) proliferate and produce cytokines such as hepatocyte growth factor (HGF) and transforming growth factor b (TGF-b), which inhibit T cell functions and prevent GvHD. Based on these findings, we have just found that low-dose total body irradiation (≤ 5Gy) followed by repeated DLI in conjunction with IBM-BMT can eradicate malignant tumors in small animals. We believe that this strategy is applicable to humans.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in plenary session 901 (Immunobiology).