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, Robert E. Hawkins

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 THF-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.

Original languageEnglish
Pages (from-to)4428-4439
Number of pages12
JournalOncotarget
Volume6
Issue number6
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Survival
T-Lymphocytes
Interleukin-6
Interleukin-2
naptumomab estafenatox
Therapeutics
Interleukin-10
Antibodies
Neoplasms

Keywords

  • ABR-217620
  • Immune analysis
  • Naptumomab estafenatox
  • Overall survival
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

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

In: Oncotarget, Vol. 6, No. 6, 2015, p. 4428-4439.

Research output: Contribution to journalArticle

Elkord, Eyad ; Burt, Deborah J. ; Sundstedt, Anette ; Nordle, Örjan ; Hedlund, Gunnar ; Hawkins, Robert E. / 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. In: Oncotarget. 2015 ; Vol. 6, No. 6. pp. 4428-4439.
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