Role of soluble CTLA-4 in controlling immune responses in melanoma
Research type
Research Study
Full title
Targeting the soluble isoform of CTLA-4 – supporting a novel therapeutic strategy in malignant melanoma
IRAS ID
71820
Contact name
Frank J. Ward
Contact email
Sponsor organisation
University of Aberdeen
Research summary
Malignant melanoma is a skin cancer for which there is an urgent need to develop more effective therapy. CTLA-4 is an inhibitory receptor on T cells and in some metastatic melanoma patients, blockade of its activity with anti-CTLA-4 monocional antibody (mAb) can significantly improve survival.
The focus here is on a second form of CTLA-4 called soluble CTLA-4 (sCTLA-4). We have blocked function of sCTLA-4 with an anti sCTLA-4 mAb and boosted immune responses to a number of immune challenges and in a model of melanoma disease, significantly reduced disease severity. Together our data indicate that targeting and blocking sCTLA-4 may be better than the current strategy for blocking CTLA-4 activity generally. Here, we will examine whether sCTLA-4 blockade boosts melanoma patient immune responses to melanoma antigens.
White blood cells from patients with early/late stage melanoma will be cultured in vitro with melanoma associated targets (peptides) with or without sCTLA-4 blockade. Analysis of cell proliferation and cytokine signature will provide readouts for sCTLA-4 blockade effects on these responses. We will also measure sCTLA-4 serum levels from melanoma patients, and examine melanoma biopsies for the presence of sCTLA-4 + T cells.
Together these experiments will evaluate the importance of sCTLA-4 in regulating melanoma-associated immunity and provide data both for future development of an anti-sCTLA-4 mAb, JMW-3B3, as a refined, better therapy for metastatic melanoma.
REC name
North of Scotland Research Ethics Committee 1
REC reference
13/NS/0126
Date of REC Opinion
7 Oct 2013
REC opinion
Further Information Favourable Opinion