Adoptive immunotherapy with cytokine-induced killer cells generated with a new good manufacturing practice-grade protocol

Domenica Lorusso, Giovanni Scambia, Sergio Rutella, Giuseppina Bonanno, Annabella Procoli, Enrica Martinelli, Luca Pierelli, P Iudicone, D Fioravanti, C Lavorino, Ml Foddai, M Vacca, F Ipsevich, M Nuti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

24 Citazioni (Scopus)

Abstract

Abstract BACKGROUND AIMS: We have recently shown that thymoglobulin (TG) efficiently expands cytokine-induced killer (CIK) cells in combination with interferon (IFN)-γ and interleukin (IL)-2 (ITG2 protocol). It is presently unknown whether the infusion of autologous immune effector cells generated by TG, IFN-γ and IL-2 is feasible and safe. METHODS: Five patients with advanced and/or refractory solid tumors were enrolled in the present phase I/II study. Peripheral blood mononuclear cells (PBMC) collected by leukapheresis were stimulated under good manufacturing practice (GMP)-conditions with IFN-γ, followed by TG and IL-2. After 2-3 weeks in culture, a median of 4.65 × 10(6) immune effector cells per kilogram of recipient's body weight was obtained and infused intravenously. The median time from enrollment into the study to infusion of the expanded CIK cells was 30 days. RESULTS: ITG2 efficiently expanded immune effector cells that comprised both conventional natural killer (NK) cells and CD3(+) CD16(+) CD56(+) CIK cells. One patient with advanced melanoma died because of disease progression before the infusion of CIK cells. The target dose of at least 2.5 × 10(6) CIK cells/kg of recipient's body weight was reached in four out of five evaluable patients. CIK cells were administered intravenously without any measurable toxicity. In vitro, CIK cells exerted lytic activity against cervical cancer cells. The median survival was 4.5 months (range 1-13) from the first infusion of CIK cells. CONCLUSIONS: This study has highlighted the feasibility and safety of the administration of CIK cells generated with the ITG2 protocol. Whether CIK cells can help control disease burden in patients with advanced malignancies will be determined in future clinical trials.
Lingua originaleEnglish
pagine (da-a)841-850
Numero di pagine10
RivistaCytotherapy
Volume14
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Adoptive immunotherapy

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