Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma

P. Comoli, R. De Palma, S. Siena, A. Nocera, S. Basso, F. Del Galdo, R. Schiavo, O. Carminati, A. Tagliamacco, G. F. Abbate, F. Locatelli, R. Maccario, P. Pedrazzoli

Research output: Contribution to journalArticle

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Abstract

Background: The outcome of patients with nasopharyngeal carcinoma (NPC presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods: A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated. Results: CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity. Conclusions: Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.

Original languageEnglish
Pages (from-to)113-117
Number of pages5
JournalAnnals of Oncology
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2004

Fingerprint

Adoptive Transfer
Cytotoxic T-Lymphocytes
Human Herpesvirus 4
T-Lymphocytes
Immunotherapy
Immunity
Adoptive Immunotherapy
Salvage Therapy
Neoplasms
HLA Antigens
Radio
Siblings
Membrane Proteins
In Vitro Techniques
Nasopharyngeal carcinoma
Drug Therapy
Therapeutics

Keywords

  • Cellular immunotherapy
  • Cytotoxic T lymphocytes
  • Epstein-Barr virus
  • Latent membrane protein 2
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma. / Comoli, P.; De Palma, R.; Siena, S.; Nocera, A.; Basso, S.; Del Galdo, F.; Schiavo, R.; Carminati, O.; Tagliamacco, A.; Abbate, G. F.; Locatelli, F.; Maccario, R.; Pedrazzoli, P.

In: Annals of Oncology, Vol. 15, No. 1, 01.2004, p. 113-117.

Research output: Contribution to journalArticle

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abstract = "Background: The outcome of patients with nasopharyngeal carcinoma (NPC presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods: A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated. Results: CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity. Conclusions: Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.",
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AU - De Palma, R.

AU - Siena, S.

AU - Nocera, A.

AU - Basso, S.

AU - Del Galdo, F.

AU - Schiavo, R.

AU - Carminati, O.

AU - Tagliamacco, A.

AU - Abbate, G. F.

AU - Locatelli, F.

AU - Maccario, R.

AU - Pedrazzoli, P.

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AB - Background: The outcome of patients with nasopharyngeal carcinoma (NPC presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods: A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated. Results: CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity. Conclusions: Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.

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