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Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity

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Abstract

Follicular lymphoma (FL) is a disease of paradoxes—incurable but with a long natural history. We hypothesized that a combination of lymphokine-activated killer (LAK) cells and monoclonal antibodies might provide a robust synergistic treatment and tested this hypothesis in a phase II clinical trial (NCT01329354). In this trial, in addition to R-CHOP, we alternated the administration of only rituximab with rituximab and autologous LAK cells that were expanded ex vivo. Our objective was to determine the in vitro capability of LAK cells generated from FL patients to produce cytotoxicity against tumor cell lines and to determine rituximab- and obinutuzumab-induced cytotoxicity via antibody-dependent cellular cytotoxicity (ADCC) activity. We analyzed the LAK cell-induced cytotoxicity and rituximab (R)- and obinutuzumab (GA101)-induced ADCC activity. We show that LAK cells generated from FL patients induce cytotoxicity against tumor cell lines. R and GA101 enhance cytolysis through ADCC activity of LAK cells. Impaired LAK cell cytotoxicity and ADCC activity were detected in 50 % of patients. Percentage of NK cells in LAK infusions were correlated with the R- and GA101-induced ADCC. Our results indicate that the combination of R or GA101 and LAK cells should be an option as frontline maintenance therapy in patients with FL.

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Acknowledgments

The authors would like to thank Roche Pharma for generously providing the anti-CD20 (GA101) antibody. This work was supported by the Spanish Ministry of Health and Social Politics (Grant Number TRA-112). We also thank Julie Chaccour for language editing.

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    Authors and Affiliations

    1. Department of Hematology, San Pedro Hospital, Logroño, La Rioja, Spain

      Ricardo García-Muñoz & Jesus Feliu

    2. Department of Hematology, University Clinic of Navarre, Pamplona, Navarra, Spain

      Ascensión López-Díaz-de-Cerio, Carlos Panizo & Susana Inogés

    3. Lymphoproliferative Group, Health Research Institute Navarra (IDISNA), Pamplona, Navarra, Spain

      Ascensión López-Díaz-de-Cerio, Angel Panizo, Mercedes Rodríguez-Calvillo, Esther Pena, Carlos Panizo & Susana Inogés

    4. Department of Pathology, Hospital Complex Navarre, Pamplona, Navarra, Spain

      Angel Panizo

    5. Translational Research Unit, Health Research Institute Aragón, CIBER Rare Diseases, CIBERER, Zaragoza, Spain

      Pilar Giraldo

    6. Department of Hematology, Hospital Complex Navarre, Pamplona, Navarra, Spain

      Mercedes Rodríguez-Calvillo & Esther Pena

    7. Department of Hematology, University Hospital, 12 de Octubre, Madrid, Spain

      Carlos Grande

    8. Department of Hematology, University Clinic Lozano Blesa, Zaragoza, Aragón, Spain

      Mayte Olave

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    1. Ricardo García-Muñoz
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    Correspondence to Carlos Panizo.

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    Ricardo García-Muñoz and Ascensión López-Díaz-de-Cerio have contributed equally to this work.

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    García-Muñoz, R., López-Díaz-de-Cerio, A., Feliu, J. et al. Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity. Immunol Res 64, 548–557 (2016). https://doi.org/10.1007/s12026-015-8747-9

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