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Oncotarget. 2015 Feb 28;6(6):4428-39.

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.

Author information

1
Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
2
Department of Medical Microbiology & Immunology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE.
3
Biomedical Research Centre, School of Environment & Life Sciences, University of Salford, Salford, UK.
4
Active Biotech AB, Lund, Sweden.

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.

PMID:
25669986
PMCID:
PMC4414201
DOI:
10.18632/oncotarget.2922
[Indexed for MEDLINE]
Free PMC Article

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