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A New Strategy for Treatment of Malignant Tumor: Intra-Bone Marrow–Bone Marrow Transplantation Plus CD4^– Donor Lymphocyte Infusion

^a First Department of Pathology,
^b Regeneration Research Center for Intractable Diseases,
^c Center for Cancer Therapy, Kansai Medical University, Osaka, Japan

Key Words. Donor lymphocyte infusion (DLI) • Malignant tumor • Graft-versus-host disease (GvHD) • Graft-versus-tumor (GvT) effect • Intra-bone marrow–bone marrow transplantation (IBM-BMT)

Correspondence: Susumu Ikehara, M.D., Ph.D., First Department of Pathology, Kansai Medical University, 10–15 Fumizonocho, Moriguchi City, Osaka, 570-8506, Japan. Telephone: 81-6-6993-9430; Fax: 81-6-6994-8283; e-mail: ikehara{at}takii.kmu.ac.jp

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.

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				Y. Koike, Y. Adachi, Y. Suzuki, M. Iwasaki, N. Koike-Kiriyama, K. Minamino, K. Nakano, H. Mukaide, A. Shigematsu, Y. Kiyozuka, et al. Allogeneic Intrabone Marrow-Bone Marrow Transplantation plus Donor Lymphocyte Infusion Suppresses Growth of Colon Cancer Cells Implanted in Skin and Liver of Rats Stem Cells, February 1, 2007; 25(2): 385 - 391. [Abstract] [Full Text] [PDF]