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The blood endotheli...
The blood endothelial cell chamber : an innovative system to study immune responses in drug development
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- Stancic, Brina (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Department of Molecular Biology, Universidad Autónoma de Madrid, and Department of Molecular Neuropathology, Center of Molecular Biology Severo Ochoa (UAM-CSIC), Nicolás Cabrera 1, 28049 Madrid, Spain,Dejana
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- Qvarfordt, Bodil (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Dejana
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- Berglund, Magnus M. (author)
- BeMa BioConsulting AB, Törnvägen 23, 136 72 Vendelsö, Sweden
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- Brenden, Nina (author)
- Swedish Orphan Biovitrum AB, Tomtebodavägen 23A, 112 76 Solna, Sweden
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- Sydow Bäckman, Mona (author)
- Swedish Orphan Biovitrum AB, Tomtebodavägen 23A, 112 76 Solna, Sweden
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- Fransson, Moa, 1981- (author)
- Uppsala universitet,Klinisk immunologi
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- Nordling, Sofia, 1985- (author)
- Uppsala universitet,Vaskulärbiologi
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- Magnusson, Peetra (author)
- Uppsala universitet,Vaskulärbiologi,Dejana
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: International Journal of Immunopharmacology. - : Elsevier BV. - 0192-0561 .- 1879-3495. ; 90
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Abstract
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- The risk for adverse immune-mediated reactions, associated with the administration of certain immunotherapeutic agents, should be mitigated early. Infusion reactions to monoclonal antibodies and other biopharmaceuticals, known as cytokine release syndrome, can arise from the release of cytokines via the drug target cell, as well as the recruitment of immune effector cells. While several in vitro cytokine release assays have been proposed up to date, many of them lack important blood components, required for this response to occur. The blood endothelial cell chamber model is an in vitro assay, composed of freshly drawn human whole blood and cultured human primary endothelial cells. Herein, its potential to study the compatibility of immunotherapeutics with the human immune system was studied by evaluating three commercially available monoclonal antibodies and bacterial endotoxin lipopolysaccharide. We demonstrate that the anti-CD28 antibody TGN1412 displayed an adaptive cytokine release profile and a distinct IL-2 response, accompanied with increased CD3+ cell recruitment. Alemtuzumab exhibited a clear cytokine response with a mixed adaptive/innate source (IFNγ, TNFα and IL-6). Its immunosuppressive nature is observed in depleted CD3+ cells. Cetuximab, associated with low infusion reactions, showed a very low or absent stimulatory effect on proinflammatory cytokines. In contrast, bacterial endotoxin demonstrated a clear innate cytokine response, defined by TNFα, IL-6 and IL-1β release, accompanied with a strong recruitment of CD14+CD16+ cells. Therefore, the blood endothelial cell chamber model is presented as a valuable in vitro tool to investigate therapeutic monoclonal antibodies with respect to cytokine release and vascular immune cell recruitment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Immunologi
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Stancic, Brina
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Qvarfordt, Bodil
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Berglund, Magnus ...
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Brenden, Nina
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Sydow Bäckman, M ...
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Fransson, Moa, 1 ...
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Nordling, Sofia, ...
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Magnusson, Peetr ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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Uppsala University