GMP production of anti-tumor cytotoxic T-cell lines for adoptive T-cell therapy in patients with solid neoplasia

I. Turin, P. Pedrazzoli, C. Tullio, E. Montini, M. Carmela La Grotteria, R. Schiavo, C. Perotti, F. Locatelli, E. Carretto, R. Maccario, S. Siena, D. Montagna

Research output: Contribution to journalArticle

Abstract

Background: The adoptive transfer of ex vivo-induced tumor-specific T-cell lines provides a promising approach for cancer immunotherapy. We have demonstrated previously the feasibility of inducing in vitro long-term anti-tumor cytotoxic T-cell (CTL) lines directed against different types of solid tumors derived from both autologous and allogeneic PBMC. We have now investigated the possibility of producing large amounts of autologous anti-tumor CTL, in compliance with good manufacturing practices, for in vivo use. Methods: Four patients with advanced solid tumors (two sarcoma, one renal cell cancer and one ovarian cancer), who had received several lines of anticancer therapy, were enrolled. For anti-tumor CTL induction, patient-derived CD8-enriched PBMC were stimulated with DC pulsed with apoptotic autologous tumor cells (TC) as the source of tumor Ag. CTL were then restimulated in the presence of TC and expanded in an Ag-independent way. Results: Large amounts of anti-tumor CTL (range 14-20× 109), which displayed high levels of cytotoxic activity against autologous TC, were obtained in all patients by means of two-three rounds of tumor-specific stimulation and two rounds of Ag-independent expansion, even when a very low number of viable TC was available. More than 90% of effector cells were CD3+ CD8+ T cells, while CD4+ T lymphocytes and/or NK cells were less than 10%. Discussion: Our results demonstrate the feasibility of obtaining large quantities of anti-tumor specific CTL suitable for adoptive immunotherapy approaches.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalCytotherapy
Volume9
Issue number5
DOIs
Publication statusPublished - 2007

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Cell- and Tissue-Based Therapy
T-Lymphocytes
Cell Line
Neoplasms
Adoptive Immunotherapy
Adoptive Transfer
Renal Cell Carcinoma
Natural Killer Cells
Sarcoma
Ovarian Neoplasms
Immunotherapy

Keywords

  • Adoptive immunotherapy
  • Cytotoxic T cells
  • GMP
  • Solid tumors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

GMP production of anti-tumor cytotoxic T-cell lines for adoptive T-cell therapy in patients with solid neoplasia. / Turin, I.; Pedrazzoli, P.; Tullio, C.; Montini, E.; La Grotteria, M. Carmela; Schiavo, R.; Perotti, C.; Locatelli, F.; Carretto, E.; Maccario, R.; Siena, S.; Montagna, D.

In: Cytotherapy, Vol. 9, No. 5, 2007, p. 499-507.

Research output: Contribution to journalArticle

Turin, I. ; Pedrazzoli, P. ; Tullio, C. ; Montini, E. ; La Grotteria, M. Carmela ; Schiavo, R. ; Perotti, C. ; Locatelli, F. ; Carretto, E. ; Maccario, R. ; Siena, S. ; Montagna, D. / GMP production of anti-tumor cytotoxic T-cell lines for adoptive T-cell therapy in patients with solid neoplasia. In: Cytotherapy. 2007 ; Vol. 9, No. 5. pp. 499-507.
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AU - Turin, I.

AU - Pedrazzoli, P.

AU - Tullio, C.

AU - Montini, E.

AU - La Grotteria, M. Carmela

AU - Schiavo, R.

AU - Perotti, C.

AU - Locatelli, F.

AU - Carretto, E.

AU - Maccario, R.

AU - Siena, S.

AU - Montagna, D.

PY - 2007

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AB - Background: The adoptive transfer of ex vivo-induced tumor-specific T-cell lines provides a promising approach for cancer immunotherapy. We have demonstrated previously the feasibility of inducing in vitro long-term anti-tumor cytotoxic T-cell (CTL) lines directed against different types of solid tumors derived from both autologous and allogeneic PBMC. We have now investigated the possibility of producing large amounts of autologous anti-tumor CTL, in compliance with good manufacturing practices, for in vivo use. Methods: Four patients with advanced solid tumors (two sarcoma, one renal cell cancer and one ovarian cancer), who had received several lines of anticancer therapy, were enrolled. For anti-tumor CTL induction, patient-derived CD8-enriched PBMC were stimulated with DC pulsed with apoptotic autologous tumor cells (TC) as the source of tumor Ag. CTL were then restimulated in the presence of TC and expanded in an Ag-independent way. Results: Large amounts of anti-tumor CTL (range 14-20× 109), which displayed high levels of cytotoxic activity against autologous TC, were obtained in all patients by means of two-three rounds of tumor-specific stimulation and two rounds of Ag-independent expansion, even when a very low number of viable TC was available. More than 90% of effector cells were CD3+ CD8+ T cells, while CD4+ T lymphocytes and/or NK cells were less than 10%. Discussion: Our results demonstrate the feasibility of obtaining large quantities of anti-tumor specific CTL suitable for adoptive immunotherapy approaches.

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