Background and Objectives. Natural killer (NK) cells constitute an important area of research for hematologic malignancies. The anti-leukemic activity of NK cells against acute myeloid leukemia (AML) blasts has been described, but very few data are available for acute lymphoid leukemia (ALL). The present study was designed to investigate whether: (i) NK effectors could be expanded from adult and pediatric ALL patients in complete remission; (ii) the signal transduction machinery of these cells was preserved; (iii) NK cells showed cytotoxic activity against autologous blasts; (iv) interleukin (IL)-2, IL-12 and IL-15 were able to increase lytic activity in our in vitro model; (v) any differences in cytotoxic activity could be found between expanded effectors from adult and pediatric patients. Design and Methods. We co-cultured patients' peripheral blood mononuclear cells (PBMC) with the feeder cell line RPMI 8866 and analyzed the NK cells' expansion capacity by cell counting and cytofluorimetric analyses. Signal transduction of expanded effector cells was evaluated by Western blot. Cr-51 release assays, before and after stimulation with activating cytokines, were performed to analyze the cytotoxic potential of effector cells against tumor cell lines and autologous blast cells. Data were analyzed with t-tests for paired data. Results. We obtained an average 40-fold increase in NK cells. Signal transduction through the CD16 receptor was preserved. Patients' expanded cells showed cytotoxic activity against target cell lines comparable to that of normal donors. More significantly, these cells also exerted a lytic effect against autologous blasts. In addition, incubating these effectors for 24 hours with IL-2 + IL-15 significantly increased this cytotoxic function. No differences in expansion and cytotoxic activity were found between pediatric and adult patients. Interpretation and Conclusions. These findings document for the first time the possibility of expanding ex vivo cytotoxic effectors with autologous killing capacity from ALL patients in remission, and suggest a new potential immunotherapeutic strategy for the management of early disease recurrence or of residual disease. (c) 2005 Ferrata Storti Foundation.

Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission / Torelli, Giovanni Fernando; Guarini, Anna; Maggio, Roberta; C., Alfieri; A., Vitale; Foa, Roberto. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 90:6(2005), pp. 785-792.

Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission

TORELLI, Giovanni Fernando;GUARINI, Anna;MAGGIO, ROBERTA;FOA, Roberto
2005

Abstract

Background and Objectives. Natural killer (NK) cells constitute an important area of research for hematologic malignancies. The anti-leukemic activity of NK cells against acute myeloid leukemia (AML) blasts has been described, but very few data are available for acute lymphoid leukemia (ALL). The present study was designed to investigate whether: (i) NK effectors could be expanded from adult and pediatric ALL patients in complete remission; (ii) the signal transduction machinery of these cells was preserved; (iii) NK cells showed cytotoxic activity against autologous blasts; (iv) interleukin (IL)-2, IL-12 and IL-15 were able to increase lytic activity in our in vitro model; (v) any differences in cytotoxic activity could be found between expanded effectors from adult and pediatric patients. Design and Methods. We co-cultured patients' peripheral blood mononuclear cells (PBMC) with the feeder cell line RPMI 8866 and analyzed the NK cells' expansion capacity by cell counting and cytofluorimetric analyses. Signal transduction of expanded effector cells was evaluated by Western blot. Cr-51 release assays, before and after stimulation with activating cytokines, were performed to analyze the cytotoxic potential of effector cells against tumor cell lines and autologous blast cells. Data were analyzed with t-tests for paired data. Results. We obtained an average 40-fold increase in NK cells. Signal transduction through the CD16 receptor was preserved. Patients' expanded cells showed cytotoxic activity against target cell lines comparable to that of normal donors. More significantly, these cells also exerted a lytic effect against autologous blasts. In addition, incubating these effectors for 24 hours with IL-2 + IL-15 significantly increased this cytotoxic function. No differences in expansion and cytotoxic activity were found between pediatric and adult patients. Interpretation and Conclusions. These findings document for the first time the possibility of expanding ex vivo cytotoxic effectors with autologous killing capacity from ALL patients in remission, and suggest a new potential immunotherapeutic strategy for the management of early disease recurrence or of residual disease. (c) 2005 Ferrata Storti Foundation.
2005
all; autologous blasts; cytotoxicity; immunotherapy; nk
01 Pubblicazione su rivista::01a Articolo in rivista
Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission / Torelli, Giovanni Fernando; Guarini, Anna; Maggio, Roberta; C., Alfieri; A., Vitale; Foa, Roberto. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 90:6(2005), pp. 785-792.
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/361672
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 40
  • ???jsp.display-item.citation.isi??? 30
social impact