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CANCER STEM CELLS

Allogeneic Intrabone Marrow-Bone Marrow Transplantation plus Donor Lymphocyte Infusion Suppresses Growth of Colon Cancer Cells Implanted in Skin and Liver of Rats

^aFirst Department of Pathology,
^bDepartment of Surgery,
^cRegeneration Research Center for Intractable Diseases, and
^dSecond Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan

Key Words. Intrabone marrow-bone marrow transplantation • Donor lymphocyte infusion • Colorectal carcinoma • RatLiver metastasis

Correspondence: Susumu Ikehara, M.D., Ph.D., First Department of Pathology, Kansai Medical University, 10-15 Moriguchi, Osaka, Japan. Telephone: 81-66-993-1001, ext. 2470; Fax: 81-66-994-8283; e-mail: ikehara{at}takii.kmu.ac.jp

Received April 17, 2006; accepted for publication October 11, 2006.


We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4⁺ cell-depleted spleen cells (CD4^– cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4^– cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell-depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4⁺ cell-depleted spleen cells (CD4^– cells) or CD8⁺ cell-depleted spleen cells (CD8^– cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8^– cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4^– cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4^– cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4^– cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4^– cells could become a new strategy for the treatment of solid tumors.

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