A63: Evidence for safety of a tumour-specific IgE antibody therapeutic candidate for ovarian cancer immunotherapy in the presence of soluble circulating tumour-associated antigen

Heather Bax1,Debra Josephs1,Sarah Rudman2,Louise Saul1,Giulia Pellizzari1,Paul Jones3,Claire Barton3,Ana Montes2,Hannah Gould1,James Spicer1,Sophia Karagiannis1

1King’s College London, London, UK,2Guy’s and St Thomas’ NHS Foundation Trust, London, UK,3Cancer Research UK, London, UK

Presenting date: Monday 2 November
Presenting time: 12.20-13.10

Background

Nearly all therapeutic antibodies used against solid tumours are of one antibody class, namely IgG. Efficacy may be improved by the development of tumour antigen-specific IgE antibodies. MOv18 IgE, targeting folate receptor-? (FR?), a surface antigen expressed by 90% of ovarian carcinomas and other tumours, is currently in pre-clinical development. FR? is shed into the circulation of patients, but it is not known what impact this soluble antigen, or the autoantibodies to FR?, will have on the safety and on the efficacy of MOv18 IgE.

Method

ELISAs have been developed to quantify the levels of human FR? and anti-FR? IgG autoantibodies in the serum of ovarian carcinoma patients and healthy volunteers. Patient serum samples and immune cells were tested in functional assays to afford an early evaluation of the in vitro safety of MOv18 IgE in the presence of soluble target antigen, FR?, and autoantibodies to FR?.

Results

Elevated levels of serum FR? were detected in tumour-bearing patients compared to healthy volunteers. Raised soluble FR? was observed in patients with FIGO stage III and IV ovarian carcinoma and those with both primary and recurrent disease, and elevated levels negatively correlated with progression free and overall survival. Some patients had detectable levels of IgG autoantibodies against FR?. However, neither serum from healthy volunteers, nor from patients, stimulated mast cell degranulation or basophil activation in the presence of MOv18 IgE.

Conclusion

Elevation of FR? in the serum of patients with ovarian carcinoma has been observed. In vitro studies using these serum samples demonstrate that MOv18 IgE does not induce activation of circulating effector cells that may contribute to type I hypersensitivity reactions. Further investigation of the changes to serum FR? levels during conventional cancer therapies and the impact of serum FR? levels on the therapeutic efficacy of MOv18 IgE are underway.