Human IgG3 with extended half-life does not improve Fc-gamma receptor-mediated cancer antibody therapies in mice.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Einarsdottir, Helga K
van Egmond, Marjolein
MetadataShow full item record
CitationHuman IgG3 with extended half-life does not improve Fc-gamma receptor-mediated cancer antibody therapies in mice. 2017, 12 (5):e0177736 PLoS ONE
AbstractCurrent anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models. Nonetheless, no therapeutic human IgG3 mAbs have been developed due to the short in vivo half-life of most known IgG3 allotypes. In this manuscript, we compared the efficacy of V-gene matched IgG1 and IgG3 anti-tumour mAb (TA99) in mice, using natural variants of human IgG3 with short- or long half-life, differing only at position 435 with an arginine or histidine, respectively.
In vitro human IgG1 and IgG3 did not show any differences in opsonisation ability of B16F10-gp75 mouse melanoma cells. IgG1, however, was superior in inducing phagocytosis of tumour cells by mouse macrophages. Similarly, in a mouse peritoneal metastasis model we did not detect an improved effect of IgG3 in preventing tumour outgrowth. Moreover, replacing the arginine at position 435 for a histidine in IgG3 to enhance half-life did not result in better suppression of tumour outgrowth compared to wild type IgG3 when injected prior to tumour cell injection.
In conclusion, human IgG3 does not have improved therapeutic efficacy compared to human IgG1 in a mouse tumour model.
DescriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files
RightsArchived with thanks to PloS one
- Section 1C: Assessment of the functional activity and IgG Fc receptor utilisation of 64 IgG Rh monoclonal antibodies. Coordinator's report.
- Authors: Kumpel BM, Beliard R, Brossard Y, Edelman L, de Haas M, Jackson DJ, Kooyman P, Ligthart PC, Monchâtre E, Overbeeke MA, Puillandre P, de Romeuf C, Wilkes AM
- Issue date: 2002 Jan
- Human monoclonal anti-D antibodies. II. The relationship between IgG subclass, Gm allotype and Fc mediated function.
- Authors: Kumpel BM, Wiener E, Urbaniak SJ, Bradley BA
- Issue date: 1989 Mar
- Anti-tumor activity of human IgG1 anti-gp75 TA99 mAb against B16F10 melanoma in human FcgammaRI transgenic mice.
- Authors: Boross P, Jansen JH, van Tetering G, Nederend M, Brandsma A, Meyer S, Torfs E, van den Ham HJ, Meulenbroek L, de Haij S, Leusen JH
- Issue date: 2014 Aug
- Distinctive role of IgG1 and IgG3 isotypes in Fc gamma R-mediated functions.
- Authors: Rozsnyay Z, Sármay G, Walker M, Maslanka K, Valasek Z, Jefferis R, Gergely J
- Issue date: 1989 Apr
- Induction of mouse IgG2a- and IgG3-dependent cellular cytotoxicity in human monocytic cells (U937) by immune interferon.
- Authors: Akiyama Y, Lubeck MD, Steplewski Z, Koprowski H
- Issue date: 1984 Nov