IgE antibody immunotherapy of solid tumours: A novel model targeting folate receptor with MOv18 IgE
Year: 2008
Session type: Poster / e-Poster / Silent Theatre session
1Division of Cancer studies, King's College London at Guy's Hospital, London, UK, 2Randall Institute, Division of Cell and Molecular Biophysics, King's College London at Guy's Hospital, London, UK, 3Division of Genetics and Molecular Medicine, King's College London at Guy's Hospital, London, UK
Abstract
Background
Several IgG antibodies are approved for clinical use in cancer. Evidence now suggests that the use of IgE antibodies, which have higher affinity for their receptors and a longer tissue half-life, may be effective against solid tumours. The chimaeric antibody MOv18 IgE against the human folate binding protein (FBP) has shown superior efficacy compared to the corresponding IgG1 in xenograft models. To explore the potential for anaphylaxis as toxicity we are now investigating the safety of this approach using an in vitro mast cell degranulation model.
Method
Degranulation assays were performed using the rat basophilic leukaemia mast cell line RBL SX-38 transfected with the human high affinity IgE receptor FcεRI and sensitised with MOv18 IgE or a control antibody. Degranulation was tested by exposure of cells to purified FBP or FBP-expressing tumour cells and measured using a β-hexosaminidase release assay.
Results
The monovalent interaction between MOv18 IgE and FBP does not trigger mast cell degranulation in vitro at concentrations of 1-1000ng/ml, suggesting that circulating soluble FBP will not trigger anaphylaxis. However, FBP-expressing tumour cells cause mast cell degranulation in an antibody-antigen specific manner, suggesting that effector cells can be activated to selectively target tumour cells.
Conclusion
We have previously demonstrated the superior efficacy of MOv18 IgE antibody over its counterpart, IgG, in pre-clinical models. Our work suggests both safety as well as efficacy of this antibody in an accepted in vitro system. Further studies leading to a phase 1 trial are now planned.
Background
Several IgG antibodies are approved for clinical use in cancer. Evidence now suggests that the use of IgE antibodies, which have higher affinity for their receptors and a longer tissue half-life, may be effective against solid tumours. The chimaeric antibody MOv18 IgE against the human folate binding protein (FBP) has shown superior efficacy compared to the corresponding IgG1 in xenograft models. To explore the potential for anaphylaxis as toxicity we are now investigating the safety of this approach using an in vitro mast cell degranulation model.
Method
Degranulation assays were performed using the rat basophilic leukaemia mast cell line RBL SX-38 transfected with the human high affinity IgE receptor FcεRI and sensitised with MOv18 IgE or a control antibody. Degranulation was tested by exposure of cells to purified FBP or FBP-expressing tumour cells and measured using a β-hexosaminidase release assay.
Results
The monovalent interaction between MOv18 IgE and FBP does not trigger mast cell degranulation in vitro at concentrations of 1-1000ng/ml, suggesting that circulating soluble FBP will not trigger anaphylaxis. However, FBP-expressing tumour cells cause mast cell degranulation in an antibody-antigen specific manner, suggesting that effector cells can be activated to selectively target tumour cells.
Conclusion
We have previously demonstrated the superior efficacy of MOv18 IgE antibody over its counterpart, IgG, in pre-clinical models. Our work suggests both safety as well as efficacy of this antibody in an accepted in vitro system. Further studies leading to a phase 1 trial are now planned.
