Annals of Oncology 9:S129-S132, 1998
© 1998 European Society for Medical Oncology
Reviews |
Treatment of relapsed Hodgkin's disease using EBV-specific cytotoxic T cells
1 Department of Pediatrics-Hematology/Oncology, Baylor College of Medicine Houston, TX, USA
2 Instilut fur Experimentelle Cliirugie, Technische Unirersilal Miinchen Germany
3 Department of Pediatrics, Sapporo Medical University
4 St. Jude Children's Research Hospital Memphis, TN, USA
Correspondence to: C.M. Rooney. Ph.D. Baylor College of Medicine, Center for Cell and Gene Therapy, 1102 Bates Street. Suite 1230.02, Houston, TX 77030, USA
Donor-derived Epstein–Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) are successful in the prevention and treatment of Epstein–Barr virus (EBV)-associated lymphoprolifer-ative disease (LPD) in allogeneic bone marrow transplant (BMT) recipients [1, 2]. This finding prompted us to use a similar approach to the treatment of relapsed EBV-positive Hodgkin's disease [3]. Autologous EBV-specific CTL lines could be generated on the first or second attempt from 11 of 15 patients with Hodgkin's disease. Peripheral blood TCR 
-chain levels were low, but increased in the activated CTL lines. Three patients have received gene-marked autologous CTL. The first two patients experienced alleviation of stage B symptoms and a drop in peripheral blood EBV load. However, this situation reversed between 6 and 12 weeks after infusion, when chemotherapy and radiation were reinstated. Both patients eventually progressed and died. The third patient had a pleural effusion, which increased after CTL infusion. Analysis of the pleural effusion revealed both tumor cells and levels of marker gene over 100 fold greater than in peripheral blood. The infused CTL line showed activity against LMP2. The patient initially improved and then remained stable for over eight months after CTL infusion, but now has progressive disease. We currently are evaluating methods for introducing the LMP2 gene into dendritic cells and using these to present LMP2 to autologous T cells. Using both retrovirus and herpesvirus vectors to express LMP2 in dendritic cells, LMP2-specific CTL were successfully generated from individuals who were EBV-sero-negative or who were non-responsive to LMP2 when presented on autologous LCL. In future protocols, LMP2-specific CTL will be used for treatment.
cytotoxic T lymphocyte (CTL), dendritic cell, Epstein–Barr virus (EBV), EBV-associated lymphoprolifer-ative disease (EBV-LPD), gene-marking, gene transfer, Hodgkin's disease, immunotherapy, latent membrane protein 2 (LMP2)