Oncotarget

Clinical Research Papers:

Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α

Eyad Elkord _, Deborah J. Burt, Anette Sundstedt, Örjan Nordle, Gunnar Hedlund and Robert E. Hawkins

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Oncotarget. 2015; 6:4428-4439. https://doi.org/10.18632/oncotarget.2922

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Abstract

Eyad Elkord1,2,3, Deborah J. Burt1, Anette Sundstedt4, Örjan Nordle4, Gunnar Hedlund4, Robert E. Hawkins1

1Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester, UK

2Department of Medical Microbiology & Immunology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE

3Biomedical Research Centre, School of Environment & Life Sciences, University of Salford, Salford, UK

4Active Biotech AB, Lund, Sweden

Correspondence to:

Eyad Elkord, e-mail: eelkord@uaeu.ac.ae, e.elkord@salford.ac.uk, eyad.elkord@manchester.ac.uk

Keywords: Renal cell carcinoma, naptumomab estafenatox, ABR-217620, immune analysis, overall survival

Received: November 18, 2014     Accepted: December 11, 2014     Published: February 14, 2015

ABSTRACT

Naptumomab estafenatox/ABR-217620/ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients’ peripheral blood. Levels of both Nap-specific CD4+ and CD8+ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects.


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