Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy

Marianna Sabatino, Seunghee Kim-Schulze, Monica C. Panelli, David Stroncek, Ena Wang, Bret Taback, Dae Won Kim, Gail DeRaffele, Zoltan Pos, Francesco M. Marincola, Howard L. Kaufman

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Purpose: High-dose interleukin-2 (IL-2) induces durable therapeutic responses in a small subset of patients with metastatic melanoma and renal cell carcinoma, but simple pretreatment predictors of response have not been identified. Patients and Methods: To identify predictive biomarkers of clinical response, sera from patients treated with high-dose IL-2 were collected for analysis using a customized, multiplex antibody-targeted protein array platform that surveyed expression of soluble factors associated with tumor immunobiology. Soluble factors associated with clinical responses were analyzed using a multivariate permutation test, and survival outcomes were determined using Kaplan-Meier and log-rank tests. Results: A training set from 10 patients identified 68 potentially relevant soluble factors that were then tested in an independent validation set of 49 patients. Class comparison revealed a cluster of 11 biomarkers that were associated with therapeutic outcome. Vascular endothelial growth factor (VEGF) and fibronectin were identified as independent predictors of response. In particular, high levels of these proteins were correlated with lack of clinical response and decreased overall survival. Conclusion: Serum VEGF and fibronectin are easily measured pretreatment biomarkers that could serve to exclude patients unlikely to respond to IL-2 therapy.

Original languageEnglish
Pages (from-to)2645-2652
Number of pages8
JournalJournal of Clinical Oncology
Issue number16
Publication statusPublished - 1 Jun 2009


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sabatino, M., Kim-Schulze, S., Panelli, M. C., Stroncek, D., Wang, E., Taback, B., Kim, D. W., DeRaffele, G., Pos, Z., Marincola, F. M., & Kaufman, H. L. (2009). Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy. Journal of Clinical Oncology, 27(16), 2645-2652.