Reactive oxygen species induced by therapeutic CD20 antibodies inhibit natural killer cell-mediated antibody-dependent cellular cytotoxicity against primary CLL cells

Werlenius, Olle (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Aurelius, Johan, 1980 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Hallner, Alexander, 1990 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Akhiani, Aliasghar, 1957 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Simpanen, Maria (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Martner, Anna, 1979 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Andersson, Per-Ola, 1964 (author)

Hellstrand, Kristoffer, 1956 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

Bergh Thorén, Fredrik, 1976 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center

(creator_code:org_t)

2016-04-16
2016
English.
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:22, s. 32046-32053

Related links:: http://www.oncotarge...; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; show less...

Abstract Subject headings

The antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells is assumed to contribute to the clinical efficacy of monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies of B cell origin. We sought to determine whether reactive oxygen species (ROS)-producing monocytes regulate the ADCC of NK cells against primary CLL cells using anti-CD20 as the linking antibody. The monoclonal CD20 antibodies rituximab and ofatumumab were found to trigger substantial release of ROS from monocytes. Antibody-exposed monocytes induced NK cell apoptosis and restricted NK cell-mediated ADCC against autologous CLL cells. The presence of inhibitors of ROS formation and scavengers of ROS preserved NK cell viability and restored NK cell-mediated ADCC against primary CLL cells. We propose that limiting the antibody-induced induction of immunosuppressive ROS may improve the anti-leukemic efficacy of anti-CD20 therapy in CLL.

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

By the author/editor: Werlenius, Olle; Aurelius, Johan, ...; Hallner, Alexand ...; Akhiani, Aliasgh ...; Simpanen, Maria; Martner, Anna, 1 ...; show more...; Andersson, Per-O ...; Hellstrand, Kris ...; Bergh Thorén, Fr ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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