Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells
Joint Authors
Ye, Shiming
Fox, Melvin I.
Belmar, Nicole A.
Sho, Mien
Chao, Debra T.
Choi, Donghee
Fang, Yuni
Zhao, Vivian
Keller, Stephen F.
Starling, Gary C.
Culp, Patricia A.
Source
Journal of Immunology Research
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-09-17
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies.
The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models.
The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor.
The involvement of effector cells was further confirmed by immunohistochemistry, which revealed strong infiltration of CD45+ effector cells into tumor xenografts in responding models, but minimal infiltration in nonresponders.
Consistent with the xenograft studies, human effector cells preferentially migrated toward in vivo-responsive tumor cells treated by enavatuzumab in vitro, with the majority of migratory cells being monocytes.
Conditioned media from enavatuzumab-treated tumor cells contained elevated levels of chemokines, which might be responsible for enavatuzumab-triggered effector cell migration.
These preclinical studies demonstrate that enavatuzumab can exert its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells.
Enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity.
American Psychological Association (APA)
Ye, Shiming& Fox, Melvin I.& Belmar, Nicole A.& Sho, Mien& Chao, Debra T.& Choi, Donghee…[et al.]. 2017. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells. Journal of Immunology Research،Vol. 2017, no. 2017, pp.1-14.
https://search.emarefa.net/detail/BIM-1181954
Modern Language Association (MLA)
Ye, Shiming…[et al.]. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells. Journal of Immunology Research No. 2017 (2017), pp.1-14.
https://search.emarefa.net/detail/BIM-1181954
American Medical Association (AMA)
Ye, Shiming& Fox, Melvin I.& Belmar, Nicole A.& Sho, Mien& Chao, Debra T.& Choi, Donghee…[et al.]. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells. Journal of Immunology Research. 2017. Vol. 2017, no. 2017, pp.1-14.
https://search.emarefa.net/detail/BIM-1181954
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1181954