Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy
Endogenous plasma IgG sets an immunological threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP)....
| Huvudupphovsmän: | , , , , , |
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| Materialtyp: | Journal article |
| Språk: | English |
| Publicerad: |
American Association for Cancer Research
2017
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| _version_ | 1826266758577651712 |
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| author | Järnum, S Runström, A Bockermann, R Winstedt, L Crispin, M Kjellman, C |
| author_facet | Järnum, S Runström, A Bockermann, R Winstedt, L Crispin, M Kjellman, C |
| author_sort | Järnum, S |
| collection | OXFORD |
| description | Endogenous plasma IgG sets an immunological threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). Here we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab) and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor seeking immune cells. |
| first_indexed | 2024-03-06T20:43:50Z |
| format | Journal article |
| id | oxford-uuid:352b58ba-0ca6-4f60-ba20-e1ee55911c00 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:43:50Z |
| publishDate | 2017 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | oxford-uuid:352b58ba-0ca6-4f60-ba20-e1ee55911c002022-03-26T13:30:37ZEnzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:352b58ba-0ca6-4f60-ba20-e1ee55911c00EnglishSymplectic Elements at OxfordAmerican Association for Cancer Research2017Järnum, SRunström, ABockermann, RWinstedt, LCrispin, MKjellman, CEndogenous plasma IgG sets an immunological threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). Here we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab) and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor seeking immune cells. |
| spellingShingle | Järnum, S Runström, A Bockermann, R Winstedt, L Crispin, M Kjellman, C Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy |
| title | Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy |
| title_full | Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy |
| title_fullStr | Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy |
| title_full_unstemmed | Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy |
| title_short | Enzymatic inactivation of endogenous IgG by IdeS enhances therapeutic antibody efficacy |
| title_sort | enzymatic inactivation of endogenous igg by ides enhances therapeutic antibody efficacy |
| work_keys_str_mv | AT jarnums enzymaticinactivationofendogenousiggbyidesenhancestherapeuticantibodyefficacy AT runstroma enzymaticinactivationofendogenousiggbyidesenhancestherapeuticantibodyefficacy AT bockermannr enzymaticinactivationofendogenousiggbyidesenhancestherapeuticantibodyefficacy AT winstedtl enzymaticinactivationofendogenousiggbyidesenhancestherapeuticantibodyefficacy AT crispinm enzymaticinactivationofendogenousiggbyidesenhancestherapeuticantibodyefficacy AT kjellmanc enzymaticinactivationofendogenousiggbyidesenhancestherapeuticantibodyefficacy |