TGF-alpha as a candidate tumor antigen for renal cell carcinomas

Sandy Pelletier, Simon Tanguay, Stephen Lee, Lakshman Gunaratnam, Nathalie Arbour, Réjean Lapointe

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Objectives: Patients with renal cell carcinomas (RCC) have few treatment options, underscoring the importance of developing new approaches such as immunotherapy. However, few tumor associated antigens (TAA), which can be targeted by immunotherapy, have been identified for this type of cancer. von Hippel-Lindau clear cell RCC (VHL-/-RCC) are characterized by mutations in the VHL tumor suppressor gene. Loss of VHL function causes the overexpression of transforming growth factor (TGF)-α, leading us to hypothesize that TGF-α could be a potential TAA for immunotherapy of kidney cancer, which was evaluated in this study. Methods and results: We first confirmed the absent or weak expression of TGF-α in important normal tissues as well as its overexpression in 61% of renal tumors in comparison to autologous normal kidney tissues. In addition, we demonstrated the immunogenicity of TGF-α, by expanding many T cell lines specific for certain TGF-α peptides or the mature TGF-α protein, when presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. Interestingly, some of these TGF-α-specific T cells were polyfunctionals and secreted IFN-γ, TNF-α and IL-2. Conclusion: We have shown that TGF-α is a valid candidate TAA, which should allow the development of a targeted immunotherapy.

Original languageEnglish (US)
Pages (from-to)1207-1218
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume58
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

    Fingerprint

Keywords

  • Cancer immunotherapy
  • Clear cell renal cell carcinoma
  • Polyfunctional antigen-specific T lymphocytes
  • Transforming growth factor (TGF)-α
  • Tumor antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Pelletier, S., Tanguay, S., Lee, S., Gunaratnam, L., Arbour, N., & Lapointe, R. (2009). TGF-alpha as a candidate tumor antigen for renal cell carcinomas. Cancer Immunology, Immunotherapy, 58(8), 1207-1218. https://doi.org/10.1007/s00262-008-0630-2