Cord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies

Niu, Qi; Wang, Wei; Li, Y.; Qin, Shaowen; Wang, Yu; Wan, Guangyu; Guan, Jian-Long; Zhu, Wenhua

doi:10.1016/j.intimp.2010.12.014

Cited by 54 publications

(44 citation statements)

References 35 publications

(40 reference statements)

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“…The application of CIK cells as adoptive immunotherapy is important in the treatment of cancer, since several clinical studies have confirmed the safety of CIK therapy for patients (12,13). Numerous clinical studies have been recently performed, whereby adjuvant infusions of CIK cells following surgical resection demonstrated a significant increase in survival time (43,44). In addition, CIK infusions were also able to reduce the viral load of hepatitis B virus (45).…”

Section: Discussionmentioning

confidence: 99%

Effect of cytokine-induced killer cells on immune function in patients with lung cancer

Pan

et al. 2016

Oncology Letters

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Abstract. Cytokine-induced killer (CIK) cells have been used as adoptive immunotherapy in cancer. The present study evaluated the effect of CIK cells on immune function in patients with lung cancer. Patients were divided into three groups, according to the treatment received prior to CIK cell treatment: CIK group (no prior treatment), Che-Sur group (prior chemotherapy and surgery) and Che-Rad group (prior chemotherapy and radiotherapy). Following treatment, the average percentage of cluster of differentiation (CD)3 + CD4 + , CD3 + , natural killer (NK) and NKT cells in peripheral blood was significantly higher than that prior to CIK treatment in the Che-Sur and CIK groups, and the levels of interferon-γ in serum were significantly higher than those prior to CIK treatment in the Che-Sur and CIK groups. On the contrary, the levels of interleukin-10 had decreased in these groups following CIK treatment. Subsequently, patients were divided into three groups according to the percentage of CD3 + CD56 + CIK cells that were administered to the patients. The number of NK and NKT cells increased with increasing number of CD3 + CD56 + cells. The patients in the CIK and Che-Sur groups were the most benefited ones following CIK treatment, contrarily to those in the Che-Rad group, since the increase in the number of CD3 + CD56 + CIK cells in the aforementioned patients enhanced the number of NK cells, which exhibit antitumor activity.

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Section: Discussionmentioning

confidence: 99%

Effect of cytokine-induced killer cells on immune function in patients with lung cancer

Pan

et al. 2016

Oncology Letters

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“…Con esta estrategia perseguimos conseguir un efecto inmunológico mediado por las células NK, a través de la reconstitución inmune y del «boost» post trasplante de células NK estimuladas ex vivo con IL15, de manera similar al objetivado en hemopatías malignas 26,27 . Sin embargo, y en vista de los resultados obtenidos con este trabajo, planteamos la inmunoterapia con células NK-IL15 como un procedimiento muy alentador en el tratamiento de tumores refractarios, incluso fuera del trasplante alogénico de donante haploidéntico [28][29][30][31][32][33][34][35] .…”

Section: Discussionunclassified

Kill the Killers: terapia con células Natural Killer en pacientes pediátricos con cáncer refractario

Quiroga¹,

Casanova²,

Martín

et al. 2012

Sanid. Mil.

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RESUMEN Introducción:En el momento actual, los tumores sólidos refractarios al tratamiento convencional constituyen la principal causa de muerte en la edad pediátrica. Por tanto, es necesario desarrollar y consolidar nuevos tratamientos. Las células Natural Killer (NK) constituyen la primera línea de defensa del sistema inmune frente al desarrollo de células tumorales. Planteamos una nueva estrategia de terapia celular antitumoral en niños con cánceres refractarios, inmunoterapia con células NK estimuladas con interleucina 15 (IL-15). Pacientes y Métodos: En 22 pacientes pediátricos con tumores sólidos refractarios y en controles sanos determinamos mediante citometría de flujo multiparamétrica y fluorescencia resuelta en el tiempo, el fenotipo y la actividad citotóxica de las células NK, respectivamente. En ratones inmunodeficientes desarrollamos un modelo de neuroblastoma metastático muy agresivo y terapia de rescate con células Natural Killer estimuladas con IL-15. Resultados: Los pacientes pediátricos con cáncer refractario tienen un mayor porcentaje de células NK bright y una menor actividad citotóxica. La estimulación con IL-15 mejora la citotoxicidad in vitro y disminuye la carga tumoral in vivo. Conclusiones: Las células NK estimuladas con IL-15 constituyen una prometedora estrategia antitumoral. INTRODUCCIÓNLos tumores sólidos en su totalidad constituyen el cáncer infantil más frecuente en la edad pediátrica 1 . Aproximadamente más de la mitad de los pacientes pediátricos con tumores sólidos tienen enfermedad avanzada a su diagnóstico 2 . Siendo el pronóstico muy desfavorable en los pacientes con enfermedad metastásica 3 . El pronóstico es particularmente pobre en los pacientes con enfermedad metastá-sica en hueso, médula ósea, y en las recaídas, donde prácticamente todos los pacientes fallecen por progresión de la enfermedad. Por ejemplo, para pacientes con Sarcoma de Ewing refractario la tasa de supervivencia a largo plazo es actualmente menor del 20% y menor del 10% si la recaída sucede dentro de los 2 primeros años 4,5 . Las estrategias de quimioterapia de segunda línea en este tipo de pacientes son realmente poco exitosas, habiéndose alcanzado el techo terapéutico. Es por esto que son necesarias nuevas aproximaciones terapéuticas que supongan una alternativa a la quimioresistencia de estos tumores.El papel del sistema inmune en el reconocimiento tumoral y en su eliminación es conocido desde hace décadas. Su potencial es tal, que la mayoría de las personas sanas eliminan células tumorales a diario gracias a un eficaz sistema inmune 6 . Se han descrito en pacientes con cáncer, alteraciones del sistema inmune adaptativo como aumento de células T reguladoras, disminución de células T CD8 efectoras, aumento de citocinas reguladoras como IL-10 7 . Sin embargo el papel del sistema inmune innato no ha sido estudiado sistemáticamente. En los últimos años el conocimiento en la inmunobiología del cáncer ha identificado a las células Natural

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“…After 21 to 28 days of culture, CD3 + CD56 + cell expansion ranges from one hundred to one thousand fold (Hoyle et al, 1998;Lu and Negrin, 1994;Schmidt-Wolf et al, 1991). Other studies have also shown that functional CIK cells can be differentiated from the MNCs of either fresh (Durrieu et al, 2013;Introna et al, 2006;Zhang et al, 2015) or banked (Pham et al, 2015) umbilical cord blood, and effectively used in combination with other treatments for, among others, the relapse of acute leukemia after cord blood transplantation (Introna et al, 2010), advanced solid malignancies after first-line chemotherapy failure (Niu et al, 2011), and esophageal cancer .…”

Section: Introductionmentioning

confidence: 99%

Culture and differentiation of cytokine-induced killer cells from umbilical cord blood-derived mononuclear cells

Duong

et al. 2016

Biomed Res Ther

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Abstract-Cytokine-induced killer cells (CIK) are cytotoxic T cells, which have both NK and T cell properties. These cells are characterized by potent, non-MHC-restricted cytotoxicity and reduced alloreactivity, which make them appealing for use in adoptive immunotherapy of cancer and virus infections. In this study, CIK cells were generated by stimulating umbilical cord blood-derived mononuclear cells (UCB-MNCs) with interferon-gamma (IFN-) on day 0. Anti-CD3 antibody and interleukin-2 (IL-2) were added after 24 hours at four different experimental concentration combinations in order to identify the optimal cytokine amounts for CIK cell proliferation. Cells were collected at four time points over a 21-day period (day 0, 7, 14, 21) for analysis of cell marker presentation using flow cytometry, as well as transcription-level cytokine production using RT-PCR. The results showed that in the 21-day culture, the average final expansion levels of CD3 + CD56 + CIK cell were in the range of hundredfold, accounted for 26% in the bulk culture. Most important, these cells strongly expressed granzyme B (80.87%), a potent factor involved in cell-mediated cytotoxicity. These CIK cells also transcriptionally overexpressed the three cytokine genes that produce IFN-, tumor necrosis factor-alpha (TNF-), and IL-2; these are key for immune cell mobilization against tumors as well as foreign pathogens. Our research establishes an effective cytokine concentration and time protocol for use in generation of CIK cells from UCB-MNCs, potentiating greater applications of CIK cell-adoptive immunotherapy in both research and clinical settings. Thus, the 3 rd and 4 th experimental conditions both stimulated CIK cell differentiation with 50 ng/ml of anti-CD3 antibody, but with IL-2 concentrations of 500 U/ml and 1000 U/ml, respectively.

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Cord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies

Cited by 54 publications

References 35 publications

Effect of cytokine-induced killer cells on immune function in patients with lung cancer

Effect of cytokine-induced killer cells on immune function in patients with lung cancer

Kill the Killers: terapia con células Natural Killer en pacientes pediátricos con cáncer refractario

Culture and differentiation of cytokine-induced killer cells from umbilical cord blood-derived mononuclear cells

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