A new strategy for treatment of malignant tumor: intra-bone marrow-bone marrow transplantation plus CD4- donor lymphocyte infusion.
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.
Suzuki
Yasuhiro
Y
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka 570-8506, Japan.
Adachi
Yasushi
Y
Minamino
Keizo
K
Zhang
Yuming
Y
Iwasaki
Masayoshi
M
Nakano
Keiji
K
Koike
Yasushi
Y
Ikehara
Susumu
S
D000818:Animals; D001835:Body Weight; D016026:Bone Marrow Transplantation / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D005354:Fibrosarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015996:Survival Rate; D016896:Treatment Outcome