Antitumor 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, Claudio Bordignon

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

The extensive exploitation of the antitumor effect of donor lymphocytes infused after allogeneic hematopoietic stem-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 antitumor effect, and control of GvHD by ganciclovir. All 17 patients evaluable for engraftment and graft-versusleukemia (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 (35%) complete remissions and 5 (29%) partial responses. The antitumor effect tightly correlated with the in vivo expansion of TK+ cells. Seven patients received ganciclovir, resulting 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.

Original languageEnglish
Pages (from-to)4698-4707
Number of pages10
JournalBlood
Volume109
Issue number11
DOIs
Publication statusPublished - 1 Jun 2007
Externally publishedYes

Fingerprint

Lymphocytes
Stem Cell Transplantation
Stem cells
Grafts
Tissue Donors
Graft vs Host Disease
Ganciclovir
Hematopoietic Stem Cell Transplantation
Immunization
Thymidine Kinase
Transplants
Viruses
Homologous Transplantation
Hematologic Neoplasms
Simplexvirus
Suicide
Genes
Technology
Safety
Recurrence

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Ciceri, F., Bonini, C., Marktel, S., Zappone, E., Servida, P., Bernardi, M., ... Bordignon, C. (2007). Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood, 109(11), 4698-4707. https://doi.org/10.1182/blood-2006-05-023416

Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. / Ciceri, Fabio; Bonini, Chiara; Marktel, Sarah; Zappone, Elisabetta; Servida, Paolo; Bernardi, Massimo; Pescarollo, Alessandra; Bondanza, Attilio; Peccatori, Jacopo; Rossini, Silvano; Magnani, Zulma; Salomoni, Monica; Benati, Claudia; Ponzoni, Maurilio; Callegaro, Luciano; Corradini, Paolo; Bregni, Marco; Traversari, Catia; Bordignon, Claudio.

In: Blood, Vol. 109, No. 11, 01.06.2007, p. 4698-4707.

Research output: Contribution to journalArticle

Ciceri, F, Bonini, C, Marktel, S, Zappone, E, Servida, P, Bernardi, M, Pescarollo, A, Bondanza, A, Peccatori, J, Rossini, S, Magnani, Z, Salomoni, M, Benati, C, Ponzoni, M, Callegaro, L, Corradini, P, Bregni, M, Traversari, C & Bordignon, C 2007, 'Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation', Blood, vol. 109, no. 11, pp. 4698-4707. https://doi.org/10.1182/blood-2006-05-023416
Ciceri F, Bonini C, Marktel S, Zappone E, Servida P, Bernardi M et al. Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood. 2007 Jun 1;109(11):4698-4707. https://doi.org/10.1182/blood-2006-05-023416
Ciceri, Fabio ; Bonini, Chiara ; Marktel, Sarah ; Zappone, Elisabetta ; Servida, Paolo ; Bernardi, Massimo ; Pescarollo, Alessandra ; Bondanza, Attilio ; Peccatori, Jacopo ; Rossini, Silvano ; Magnani, Zulma ; Salomoni, Monica ; Benati, Claudia ; Ponzoni, Maurilio ; Callegaro, Luciano ; Corradini, Paolo ; Bregni, Marco ; Traversari, Catia ; Bordignon, Claudio. / Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. In: Blood. 2007 ; Vol. 109, No. 11. pp. 4698-4707.
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