Ganciclovir-sensitive acute graft-versus-host disease in mice receiving herpes simplex virus-thymidine kinase-expressing donor T cells in a bone marrow transplantation setting
Contassot, E.; Ferrand, C.; Angonin, R.; Cohen, J.L.; de Carvalho Bittencourt, M.; Lorchel, F.; Laithier, V.; Cahn, J.Y.; Klatzmann, D.; Herve, P.; Tiberghien, P.
Transplantation 69(4): 503-508
2000
ISSN/ISBN: 0041-1337 PMID: 10708102 Document Number: 525556
Background. The use of donor T cells expressing the herpes simplex thymidine kinase (HSV-TK) gene followed by ganciclovir (GCV) treatment could allow for specific modulation of the alloreactivity occurring after bone marrow transplantation. We are presently exploring such an approach in a phase I clinical trial. Methods. To examine the beneficial effect of administrating HSV-TK-expressing donor T lymphocytes +- GCV treatment on acute graft-versus-host disease (aGVHD) control, irradiated Balb/c or C57BL/6 mice underwent transplantation with allogeneic bone marrow cells in conjunction with CD3+ allogeneic splenocytes from transgenic mice expressing an HSV-TK transgene. GCV treatment was initiated upon the occurrence of severe aGVHD. Results. GCV treatment resulted in a 40-60% long-term survival rate of GVHD-free recipients having received HSV-TK-expressing T cells, whereas only 0-6% of mice survived without GCV treatment. Lethal aGVHD occurred in all the control animals having received non-HSV-TK-expressing T cells, irrespective of GCV treatment. Conclusion. Our results demonstrate that the administration of donor HSV-TK-expressing T cells to hematopoietic stem cell graft recipients followed by GCV treatment at the onset of severe aGVHD significantly reduces aGVHD-induced mortality and results in GVHD-free surviving recipients.