Gene and cell therapy for relapsed leukemia after allo-stem cell transplantation.
To control severe GvHD while maintaining strong GvL effects in the context of allo-stem cell transplantation (allo-SCT), a phase I/II clinical trial of infusions of donor lymphocytes transduced with the herpes simplex virus thymidine kinase (TK-DLI) started at the Tsukuba University Hospital. To date, five (2 AML, 2 ALL, and 1 MDS) out of eight patients enrolled in the trial received approximately 7x10(7) transduced cells per kilogram of body weight and four patients showed some clinical responses such inhibition of the leukemic cell proliferation or mitigation of lymph node swelling. Especially, one MDS patient achieved complete remission and has remained in CR for 2 years after the treatment. GvHD developed in two patients (1 acute and 1 chronic) and the acute (grade III) was successfully controlled by administration of ganciclovir without any immunosuppressive drugs. Since HSV-TK as a strong antigen induced CTLs against transduced cells in patients, however, TK-DLI is expected to provide a more effective adoptive immune cell therapy by performance just after allo-SCT where the patient's immune function is severely damaged.
Group of Gene and Cell Therapy, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan. monodera@md.tsukuba.ac.jp
Masafumi
M
Onodera
D064987:Cell- and Tissue-Based Therapy; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000601:surgery* / Q000628:therapy*; D012008:Recurrence; D014184:Transplantation, Homologous; D017211:Treatment Failure