- Author
-
A.R. Temming
- Title
- Opsonin interactions with immunoglobulin-Fc receptors and their effector functions
- Supervisors
-
C.E. van der Schoot
- Co-supervisors
-
G. Vidarsson
- Award date
- 19 February 2021
- Number of pages
- 229
- ISBN
- 9789464191172
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
This thesis evaluates the role of opsonizing immunoglobulin G (IgG) in cellular destruction through IgG-Fc receptors (FcγRs). In disease settings, IgG features can affect and determine the magnitude of (undesired) functional responses towards target cells, and thus disease severity. Therefore, investigating these factors is of crucial importance in order to elucidate pathophysiology and understand disease manifestation, progression, and outcome.
One of the IgG attributes we address is glycosylation, particularly sialylation and fucosylation, and its effect on FcγR binding capacity and effector functions, respectively. Next to IgG glycosylation, several functional attributes of both effector- and target cells influencing IgG-mediated erythrocyte destruction are studied in detail.
The role of opsonic C-reactive protein (CRP; reportedly elevated and functionally involved in antibody-mediated pathologies) is also studied extensively in the context of IgG-mediated erythrocyte destruction and tumor cell killing. The mechanism underlying CRP’s potentiating effect on IgG-mediated processes is dissected by analyzing the role of FcγRs and IgA-Fc receptor (FcαRI) that have been designated as CRP receptors.
With the emerging knowledge on IgG structure-function relations, the amount of propositions for novel IgG-based therapeutic strategies grew. One promising antibody engineering tool for this is the generation of bispecific antibodies (bsAbs). This thesis describes a novel bsAb format aiming to augment conventional IgG-mediated tumor destruction through additional recruitment of neutrophil effector functions.
In conclusion, this thesis provides cutting-edge information on IgG/CRP-FcR interactions and functional responses. We hope that our findings will add to a better notion of antibody biology and eventually contribute to optimization of antibody-based immunotherapies. - Persistent Identifier
- https://hdl.handle.net/11245.1/f945ff50-a3bb-4c77-87fa-7ddfda42f81a
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction and scope of the thesis
Chapter 2: Human DC-SIGN and CD23 do not interact with human IgG
Chapter 3: Cross-reactivity of mouse IgG subclasses to human Fc gamma receptors: Antibody deglycosylation only eliminates IgG2b binding
Chapter 4: Functional attributes of antibodies, effector cells, and target cells affecting NK cell-mediated ADCC
Chapter 5: C-reactive protein enhances IgG-mediated cellular destruction through FcγRs
Chapter 6: Augmenting antibody-based anti-cancer therapeutics with neutrophil cytotoxicity
Chapter 7: General discussion
English summary; Nederlandse samenvatting; Abbreviations; Contributing authors; Ph.D. portfolio; List of publications; Biography; Dankwoord/Acknowledgements
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