Abstract
Cyclosporin A (CsA) has been used clinically to induce graft-versus-host disease following autologous bone marrow transplantation in an attempt to destroy residual leukemia cells and reduce relapse. To analyze the antitumor potential of murine syngeneic graft-versus-host disease (SGVHD), C3H/HeN mice were lethally irradiated, reconstituted with T cell-depleted syngeneic bone marrow (ATBM) and treated with CsA for 21 days. Graft-versus-leukemia activity was assessed by challenging groups of olive oil-treated control ATBM (OO-ATBM) and CsA-treated (CsA-ATBM) mice 1 week after CsA therapy with graded doses of the syngeneic 38C13 B cell lymphoma. Following CsA treatment, up to 70% of CsA-ATBM developed SGVHD and more than 70% of the animals injected with 500 38C13 cells exhibited long-term survival (MST > 80 days). In contrast, none of the OO-ATBM control mice developed SGVHD, and more than 75% of these mice died following injection of 500 38C13 tumor cells (MST = 34 days). Long-term survivors were not resistant to tumor challenge suggesting that tumor-specific immunity did not develop. Finally, class II negative 38C13 cells cultured in IL-4 or IL-10 were not inducible for MHC class II molecules, demonstrating that class II-independent antitumor mechanisms exist in SGVHD mice.
Original language | English |
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Pages (from-to) | 363-372 |
Number of pages | 10 |
Journal | Bone Marrow Transplantation |
Volume | 23 |
Issue number | 4 |
DOIs | |
State | Published - 1999 |
Bibliographical note
Funding Information:This work was supported in part by a Research Scholar Grant from the Council for Tobacco Research-USA, Inc (JSB) and Grant AI31998 from the National Institutes of Health (JSB).
Keywords
- Cyclosporin A
- Graft-versus-host disease
- Graft-versus-tumor
- Syngeneic bone marrow transplantation
ASJC Scopus subject areas
- Hematology
- Transplantation