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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4698-4707. Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-05-023416. This Article Full Text (PDF) All Versions of this Article: blood-2006-05-023416v1 109/11/4698    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ciceri, F. Articles by Bordignon, C. Search for Related Content PubMed PubMed Citation Articles by Ciceri, F. Articles by Bordignon, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 17, 2006 Accepted February 8, 2007 Anti-tumor effects of HSV-TK engineered donor lymphocytes after allogeneic stem cell transplantation Fabio Ciceri, Chiara Bonini, Sarah Marktel, Elisabetta Zappone, Paolo Servida, Massimo Bernardi, Alessandra Pescarollo, Attilio Bondanza, Jacopo Peccatori, Silvano Rossini, Zulma Magnani, Monica Salomoni, Claudia Benati, Maurilio Ponzoni, Luciano Callegaro, Paolo Corradini, Marco Bregni, Catia Traversari, and Claudio Bordignon* Hematology & Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy Cancer Immunotherapy & Gene Therapy Program, San Raffaele Scientific Institute, Milan, Italy Universita Vita-Salute San Raffaele, Milan, Italy MolMed SpA, Milan, Italy Dept of Pathology, San Raffaele Scientific Institute, Milan, Italy * Corresponding author; email: c.bordignon{at}hsr.it. The extensive exploitation of the anti-tumor effect of donor lymphocytes infused after allogeneic hematopoietic cell transplantation (allo-HSCT) is limited by the risk of graft-versus-host disease (GvHD). To overcome this limitation, we investigated the therapeutic potential of donor lymphocytes engineered with the suicide gene thymidine kinase of Herpes Simplex virus (TK) in 23 patients experiencing recurrence of hematologic malignancies after allo-HSCT. Long-term follow-up of infused patients included analysis of engraftment of genetically engineered lymphocytes, in vivo assessment of anti-tumor effect and control of GvHD by ganciclovir. All 17 patients evaluable for engraftment and graft-versus-leukemia (GvL) had circulating TK+ cells detectable beginning at a median time of 18 days. Eleven patients (65%) experienced a substantial clinical benefit resulting in 6 complete remissions (35%) and 5 (29%) partial responses. The anti-tumor effect tightly correlated with the in vivo expansion of TK+ cells. Seven patients received ganciclovir that resulted in elimination of TK+ cells and effective and selective treatment of GvHD. Immunization against HSV-TK was observed in 7 patients, but did not preclude an effective GvL. These data validate the feasibility, safety and efficacy of TK+ cells in the context of allografting, and represent the basis for a broader application of this technology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Altruistic donor T cells Pierre Tiberghien Blood 2007 109: 4595. [Full Text] [PDF]

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