Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor

Daniela Montagna, Ilaria Turin, Roberta Schiavo, Enrica Montini, Nadia Zaffaroni, Raffaella Villa, Simona Secondino, Ilaria Schiavetto, Laura Caliogna, Franco Locatelli, Virginia Libri, Andrea Pession, Roberto Tonelli, Rita Maccario, Salvatore Siena, Paolo Pedrazzoli

Research output: Contribution to journalArticle

Abstract

Background aims. Adoptive T-cell therapy with tumor-specific T cells has emerged as a potentially useful approach for treating patients with advanced malignancies. We have demonstrated previously the feasibility of obtaining large numbers of autologous anti-tumor-specific cytotoxic T lymphocytes (CTL) generated by stimulation of patients' peripheral blood mononuclear cells with dendritic cells pulsed with apoptotic tumor cells. Methods. Six patients with progressing metastatic solid tumors (one renal cell carcinoma, two ovarian cancers, two extraosseous peripheral neuroectodermal tumors, one soft tissue sarcoma) not eligible for conventional therapies were treated with adoptive immunotherapy. Anti-tumor CTL, proven to be reactive in vitro against patient tumor cells, but not against normal cells, were infused following lymphodepleting chemotherapy administered to favor T-cell proliferation in vivo. Results. Patients received a median of nine CTL infusions (range 2-19). The median number of CTL administered per infusion was 11 × 108 (range 155 × 108). No patient experienced acute or late adverse events related to CTL infusion, even when large numbers of cells were given. Post-infusion laboratory investigations demonstrated an increase in the frequency of circulating anti-tumor T-cells and, in patients with a longer follow-up receiving two CTL infusions/year, a stabilization of these values. Conclusions. Our study demonstrates that autologous ex vivo-generated anti-tumor CTL can be administered safely in patients with advanced solid tumors and can improve the immunologic reactivity of recipients against tumor. These preliminary results provide a rationale for evaluating the clinical efficacy of this immunotherapeutic approach in phase I/II studies.

Original languageEnglish
Pages (from-to)80-90
Number of pages11
JournalCytotherapy
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Adoptive Immunotherapy
Cytotoxic T-Lymphocytes
Safety
Neoplasms
T-Lymphocytes
Peripheral Primitive Neuroectodermal Tumors
Lymphocyte Activation
Cell- and Tissue-Based Therapy
Renal Cell Carcinoma
Sarcoma
Ovarian Neoplasms
Dendritic Cells
Blood Cells
Cell Count
Cell Proliferation

Keywords

  • adoptive T-cell therapy
  • autologous tumor cells
  • cytotoxic T lymphocytes
  • lymphodepletion
  • solid tumors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Molecular Medicine

Cite this

Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor. / Montagna, Daniela; Turin, Ilaria; Schiavo, Roberta; Montini, Enrica; Zaffaroni, Nadia; Villa, Raffaella; Secondino, Simona; Schiavetto, Ilaria; Caliogna, Laura; Locatelli, Franco; Libri, Virginia; Pession, Andrea; Tonelli, Roberto; Maccario, Rita; Siena, Salvatore; Pedrazzoli, Paolo.

In: Cytotherapy, Vol. 14, No. 1, 01.2012, p. 80-90.

Research output: Contribution to journalArticle

Montagna, Daniela ; Turin, Ilaria ; Schiavo, Roberta ; Montini, Enrica ; Zaffaroni, Nadia ; Villa, Raffaella ; Secondino, Simona ; Schiavetto, Ilaria ; Caliogna, Laura ; Locatelli, Franco ; Libri, Virginia ; Pession, Andrea ; Tonelli, Roberto ; Maccario, Rita ; Siena, Salvatore ; Pedrazzoli, Paolo. / Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor. In: Cytotherapy. 2012 ; Vol. 14, No. 1. pp. 80-90.
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AU - Montagna, Daniela

AU - Turin, Ilaria

AU - Schiavo, Roberta

AU - Montini, Enrica

AU - Zaffaroni, Nadia

AU - Villa, Raffaella

AU - Secondino, Simona

AU - Schiavetto, Ilaria

AU - Caliogna, Laura

AU - Locatelli, Franco

AU - Libri, Virginia

AU - Pession, Andrea

AU - Tonelli, Roberto

AU - Maccario, Rita

AU - Siena, Salvatore

AU - Pedrazzoli, Paolo

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N2 - Background aims. Adoptive T-cell therapy with tumor-specific T cells has emerged as a potentially useful approach for treating patients with advanced malignancies. We have demonstrated previously the feasibility of obtaining large numbers of autologous anti-tumor-specific cytotoxic T lymphocytes (CTL) generated by stimulation of patients' peripheral blood mononuclear cells with dendritic cells pulsed with apoptotic tumor cells. Methods. Six patients with progressing metastatic solid tumors (one renal cell carcinoma, two ovarian cancers, two extraosseous peripheral neuroectodermal tumors, one soft tissue sarcoma) not eligible for conventional therapies were treated with adoptive immunotherapy. Anti-tumor CTL, proven to be reactive in vitro against patient tumor cells, but not against normal cells, were infused following lymphodepleting chemotherapy administered to favor T-cell proliferation in vivo. Results. Patients received a median of nine CTL infusions (range 2-19). The median number of CTL administered per infusion was 11 × 108 (range 155 × 108). No patient experienced acute or late adverse events related to CTL infusion, even when large numbers of cells were given. Post-infusion laboratory investigations demonstrated an increase in the frequency of circulating anti-tumor T-cells and, in patients with a longer follow-up receiving two CTL infusions/year, a stabilization of these values. Conclusions. Our study demonstrates that autologous ex vivo-generated anti-tumor CTL can be administered safely in patients with advanced solid tumors and can improve the immunologic reactivity of recipients against tumor. These preliminary results provide a rationale for evaluating the clinical efficacy of this immunotherapeutic approach in phase I/II studies.

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