AMBLor: An Innovative Prognostic Test for Early Stage Cutaneous Melanoma

Background

Cutaneous melanoma is the most lethal form of skin cancer with an increasing worldwide incidence. More than 16,000 patients are diagnosed with melanoma annually in the UK alone, placing an ever increasing demand on healthcare resources.

In the absence of a reliable means through which to accurately identify which patients with early AJCC stage I/II melanomas are at high risk of their disease progressing this means all patients require the same clinical follow up regime and attendance at outpatient clinics up to 16 times in 5 years. Moreover, in the era of melanoma precision medicine, with accumulating evidence showing early treatment results in improved patient survival, the identification of patients with early stage high risk melanomas at an earlier time point in their care pathway would facilitate appropriate stratification and potential access to life saving drug therapy regimes. Consequently, there is an unmet critical need for credible biomarkers able to identify high-risk melanoma subsets, as well as companion or stratification biomarkers to guide the most appropriate clinical follow up, including adjuvant immunotherapy.

Biomarker discovery and validation studies by the group of Professor Penny Lovat at Newcastle University led to the identification of two proteins, AMBRA1 and loricrin (AMLo) whose expression is maintained in the normal cutaneous epidermis but which are lost in the epidermis overlying high-risk early stage I melanomas. Publication of this work in The British Journal of Dermatology, and the production of a highly specific and sensitive automated immunohistochemical assay kit containing recombinant antibodies to AMBRA1 and Loricrin (produced by the Newcastle University Spin out company, AMLo Biosciences Ltd) led to the award of the 2018 NICE AdviSeME Prize to investigators,  Lovat, Labus and Ellis and the award of NIHR i4i funding (for which the Newcastle Molecular Pathology Node is a collaborating partner), to include biomarker validation and health economic studies as well as patient and public contribution. The Node has provided all of the immunostaining and validation of the new antibodies and kits, as well as blind scoring of large internationally sourced melanoma cohorts from ethical biobanks by two Node pathologists using digital imaging to link with colleagues in Cambridge, UK and Buffalo, US.

Funding

£1,005,680. National Institute for Health Research: Invention for Innovation (i4i) to PE Lovat (PI),

T Cunliffe, RA Ellis, M Labus, L Vale, J Lecouturier, NJ Reynolds, P Sloan, A Husain, N Stefanos, and

R Plummer

Purpose

To validate and support the clinical adoption of AMBLor onto clinical guidelines as an innovative prognostic test for early stage cutaneous melanoma, and the development of a business model based on a UK service provided by the Molecular Pathology Node in collaboration with AMLo Biosciences Ltd.

Main achievements / outcomes

  • Validation of AMBLor diagnostic antibodies and manufactured kit (stability testing ongoing).
  • SOP production for automated immune-histochemical staining and analysis of AMBLor in non- ulcerated early stage melanomas.
  • Establishment and transfer of powered geographically distinct cohorts of AJCC stage I/II melanomas from UK, Spain, Australia and USA with AMBLor analysis completed in UK and Spanish cohorts.
  • Generation of data to verify additional clinical utility of AMBLor as a companion biomarker for adjuvant immunotherapy for AJCC stage II melanomas.
  • Acceptance and invited presentation of data at The European Association for Dermato-Oncology (Paris 2019, best talk prize awarded to P Lovat, ASC) (Chicago 2019), The International Melanoma Working Group (Lisbon 2019), and The Society for Melanoma Research (Salt Lake City 2019).
  • Public engagement including national and international press release (September 2019).

Future direction

Complete AMBLor Validation in 2000 AJCC stage I / II melanomas and Health Economic studies (by end 2020) to support adoption onto NICE clinical guidelines. Develop commercial plan for a UK based service for AMBLor analysis and international kit distribution.