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

• Published in: Immunologic research Vol. 64; no. 2; pp. 548 - 557
• Main Authors: García-Muñoz, Ricardo, López-Díaz-de-Cerio, Ascensión, Feliu, Jesus, Panizo, Angel, Giraldo, Pilar, Rodríguez-Calvillo, Mercedes, Grande, Carlos, Pena, Esther, Olave, Mayte, Panizo, Carlos, Inogés, Susana
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2016; Springer Nature B.V
• Subjects: Allergology; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - pharmacology; Antibody-Dependent Cell Cytotoxicity - immunology; Antineoplastic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Cellular biology; Chemotherapy; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Humans; Immune system; Immunology; Internal Medicine; Killer Cells, Lymphokine-Activated - immunology; Killer Cells, Lymphokine-Activated - metabolism; Lymphocyte Count; Lymphoma; Lymphoma, Follicular - diagnosis; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - immunology; Lymphoma, Follicular - metabolism; Medicine/Public Health; Original Article; Phenotype; Rituximab - immunology; Rituximab - pharmacology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Time Factors; Follicular lymphoma (FL); Rituximab (R); Obinutuzumab (GA101); Antibody-dependent cellular cytotoxicity (ADCC); Lymphokine-activated killer (LAK) cells; Natural killer cells (NK)
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-015-8747-9

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.