IgE-mediated immunotherapy in non-haematopoietic malignancies

IgE antibodies are effectively transported from the circulation into tissues, where IgE receptors on IgE effector cells are in place to mount strong immune responses against cancer cells. To take advantage of this unique property of IgE to home and persist in tissues, we are developing immunotherapeutic strategies, based on IgE-linked tumour cell targeting and killing for the treatment of non-haematopoietic cancers. We demonstrate that recombinant tumour antigen-specific IgE antibodies are capable of targeting human effector cells such as monocytes and eosinophils to kill tumour cells. Our recombinant anti-folate binding protein (FBP) IgE antibody, MOv18 IgE, inhibits tumour cell growth in our mouse xenograft models of human ovarian carcinoma: this inhibition is associated with infiltration of human monocytes into the tumours, resulting in prolonged survival of tumour-bearing mice.

We have recently been investigating the mechanisms by which peripheral blood mononuclear cells kill tumour cells in vitro and in vivo. Experiments are now in progress to further explore the potential mechanisms employed by IgE antibodies to ovarian, melanoma and breast tumour markers to activate effector cells against tumour cells. Our findings aim to establish the basis of a strategy for the potential use of tumour-specific IgE antibodies as treatments in these malignant diseases.