title: Potential for monocyte recruitment by IgE immunotherapy for cancer in a rat model of tumour metastasis.
abstract: BACKGROUND
  Nearly all anti-tumour antibodies are of a single class-namely, IgG. Efficacy might be improved by development of tumour-specific IgE antibodies, which have higher affinities for effector cell receptors and perform potent immune functions. MOv18IgE, which targets folate receptor α (FRα), is a novel system to model this hypothesis. Human chimeric MOv18 IgE has shown superior efficacy in two murine xenograft models compared with MOv18 IgG1. Our aim was to examine the potential of this antibody class to activate monocytes.
  
  
  METHODS
  We developed an immunocompetent rat model system of rat tumour lung metastases expressing human FRα, and engineered surrogate rat MOv18 IgE and IgG antibodies to assess their efficacy and ability to recruit monocytes in the rat model system.
  
  
  RESULTS
  In-vivo assessment of the efficacy of rat MOv18 IgE demonstrated superior tumour growth restriction compared with rat MOv18 IgG (tumour occupancy 6·8% [SE 1·6] vs 16·0 [1·7]; p<0·0001). We measured significant CD68-positive (CD68+) macrophage infiltration of tumours after MOv18 IgE treatment (mean ratio of CD68+ cells in tumour vs periphery 3·6 [0·5] for MOv18 IgE-treated tumours vs 2·3 [0·3] for MOv18 IgG-treated tumours; p=0·03).
  
  
  CONCLUSIONS
  Our in-vivo studies using rat MOv18 IgE show the importance of monocyte recruitment in the efficacy of this antibody, and provide further evidence that tumour-specific IgE antibodies might offer improved efficacy against cancer by recruiting key immune effector cells.
  
  
  BACKGROUND
  Academy of Medical Sciences Starter Grant, Cancer Research UK New Agents Committee Grant.
authors: St John's Institute of Dermatology, King's College London, London, UK; Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address: debra.josephs@kcl.ac.uk.
authors: Debra H
authors: DH
authors: Josephs
authors: St John's Institute of Dermatology, King's College London, London, UK.
authors: Heather J
authors: HJ
authors: Bax
authors: Cancer Research UK, Biotherapeutics Unit, South Mimms, UK.
authors: Heike
authors: H
authors: Lentfer
authors: Cancer Research UK, Biotherapeutics Unit, South Mimms, UK.
authors: Chris
authors: C
authors: Selkirk
authors: Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors: James F
authors: JF
authors: Spicer
authors: St John's Institute of Dermatology, King's College London, London, UK.
authors: Sophia N
authors: SN
authors: Karagiannis