A syndrome similar to GVHD can be induced with cyclosporine (CsA) in animal models of autologous GVHD. The animal studies suggest that this syndrome generates antitumor activity similar to that seen with allogeneic GVHD. Autologous GVHD can also be induced with CsA in patients, and preliminary data suggest that this syndrome generates antitumor activity similar to that seen with allogeneic GVHD. Autologous GVHD can also produce a clinically significant antitumor effect. The mechanisms responsible for the antitumor activity of autologous GVHD will be investigated in the animal model. Specifically, the target antigens and effector cells responsible for the antitumor activity will be defined. Since autologous GVHD is a mild, self-limited disease, it should be possible to enhance the antitumor activity without increasing toxicity. Strategies for enhancing the antitumor effect of autologous GVHD, either by stimulating effector cells with IL-2, IL-4 or IL-6 or by upregulating target antigen expression with cytokines, will also be explored in the animal model. The animal results will be applied to designing studies into the mechanisms responsible for, and techniques for enhancing, the antitumor effect of autologous GVHD in an in vitro model which uses explanted tumor and effector cells from patients undergoing autologous GVHD induction. Techniques developed from the preclinical studies for enhancing the antitumor activity of autologous GVHD will be tested in clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054203-05
Application #
2095741
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Ruvolo, P P; Fischer, A C; Vogelsang, G B et al. (1995) Analysis of the V beta T-cell receptor repertoire in autologous graft-versus-host disease. Ann N Y Acad Sci 756:432-4
Ruvolo, P; Bright, E; Kennedy, M J et al. (1995) Cyclosporine-induced autologous graft versus host disease: assessment of cytolytic effector mechanisms and the V beta T-cell receptor repertoire. Transplant Proc 27:1363-5
Hess, A D; Kennedy, M J; Ruvolo, P P et al. (1995) Antitumor activity of syngeneic/autologous graft-versus-host disease. Ann N Y Acad Sci 770:189-202
Vogelsang, G B; Hess, A D (1994) Graft-versus-host disease: new directions for a persistent problem. Blood 84:2061-7
Hess, A D; Fischer, A C; Horwitz, L et al. (1994) Characterization of peripheral autoregulatory mechanisms that prevent development of cyclosporin-induced syngeneic graft-versus-host disease. J Immunol 153:400-11
Kennedy, M J; Vogelsang, G B; Jones, R J et al. (1994) Phase I trial of interferon gamma to potentiate cyclosporine-induced graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer. J Clin Oncol 12:249-57
Yeager, A M; Vogelsang, G B; Jones, R J et al. (1993) Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation for acute myeloid leukemia. Leuk Lymphoma 11:215-20
Hess, A D; Jones, R C; Santos, G W (1993) Autologous graft-vs-host disease: mechanisms and potential therapeutic effect. Bone Marrow Transplant 12 Suppl 3:S65-9
Kennedy, M J; Vogelsang, G B; Beveridge, R A et al. (1993) Phase I trial of intravenous cyclosporine to induce graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer. J Clin Oncol 11:478-84
Yeager, A M; Wagner Jr, J E; Graham, M L et al. (1992) Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation. Blood 80:2425-8

Showing the most recent 10 out of 14 publications