A new strategy for treatment of malignant tumor: intra-bone marrow-bone marrow transplantation plus CD4- donor lymphocyte infusion

Stem Cells. 2005 Mar;23(3):365-70. doi: 10.1634/stemcells.2004-0258.

Abstract

Donor lymphocyte infusion (DLI) is clinically used for the treatment of malignant tumors. We have found recently that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to treat various autoimmune diseases, even when radiation doses are reduced. In addition, recently we have found that IBM-BMT can prevent not only graft failure but also graft-versus-host disease (GvHD). Based on these findings, we attempted to prevent and treat the progression of a tumor (Meth-A cell line: BALB/c-derived fibrosarcoma) by DLI plus IBM-BMT. When the tumors had grown to approximately 10 x 10 mm, the tumor-bearing BALB/c (H-2(d)) mice were irradiated with 5 Gy, and whole spleen cells from C57BL/6J (B6) (H-2(b)) mice (as DLI) were then intravenously injected into the BALB/c mice. Simultaneously, bone marrow cells (BMCs) from B6 mice were injected directly into the bone marrow cavity of the BALB/c mice (IBM-BMT). The tumors decreased in size, but the mice died of GvHD. However, when CD4(+) T-cell-depleted spleen cells were used for DLI, the recipients showed only mild GvHD and survived longer, due to the slow growth of the tumor. In contrast, when CD8(+) T-cell-depleted spleen cells were used for DLI, the recipients showed more severe GvHD than those injected with whole spleen cells. These results suggest that IBM-BMT plus DLI (the depletion or reduction of a certain cell population like CD4(+) T cells) could be helpful to suppress both GvHD and tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Bone Marrow Transplantation / methods*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / transplantation*
  • Fibrosarcoma / mortality
  • Fibrosarcoma / pathology
  • Fibrosarcoma / therapy*
  • Graft vs Host Disease / immunology
  • Graft vs Tumor Effect / immunology
  • Lymphocyte Depletion
  • Lymphocyte Transfusion / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Sarcoma, Experimental / mortality
  • Sarcoma, Experimental / pathology
  • Sarcoma, Experimental / therapy
  • Spleen / cytology
  • Spleen / immunology
  • Survival Rate
  • Treatment Outcome