Simultaneous ligation of CD5 and CD28 with monoclonal antibodies restores impaired immunostimulatory function in human renal cell carcinoma

Jonathan Lindner, Flordeliza S. Villanueva, John M. Dent, Kevin Wei, Jiri Sklenar, Sanjiv Kaul

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Tumor cells, including renal cell carcinoma (RCC) cells, do not effectively stimulate T lymphocyte responses against specific antigens presented on their surface. Reasons for this low immunogenicity may include low or absent expression of MHC class I and/or class II molecules, as well as accessory and costimulatory molecules. We used tumor cell pretreatment with cytokines, together with monoclonal antibodies (mAbs) directed at receptors for costimulatory molecules, to render RCC cells immunostimulatory. Interferon-γ or tumor necrosis factor-α pretreatment enhanced expression of MHC class I and class II molecules, as well as CD54, but had only minimal effects on T cell activation. A CD28 mAb, or an even more effective combination of CD28 and CD5 mAb, induced strong primary proliferative responses of allogeneic resting T lymphocytes. Cytokine pretreatment further augmented this T cell response in vitro and allowed T cell expansion and establishment of T cell lines. Stimulation of T cells with autologous RCC cells resulted in a similar T cell activation but with the expansion of cytolytic T cells directed at autologous MHC class II molecules. These experiments demonstrate that cytokines combined with costimulatory mAbs are useful for increasing the immunogenicity of tumor cells. They also indicate, however, that autologous MHC class II expression on tumor cells, together with strong costimulation, may lead to the activation of autoreactive T cells.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalUrological Research
Volume29
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Ligation
Monoclonal Antibodies
T-Lymphocytes
Cytokines
Neoplasms
Interferons
Tumor Necrosis Factor-alpha
Antigens
Cell Line

Keywords

  • Autoimmunity
  • CD5 and CD28
  • Costimulation
  • Renal cell cancer
  • Tumor immunology

ASJC Scopus subject areas

  • Urology

Cite this

Simultaneous ligation of CD5 and CD28 with monoclonal antibodies restores impaired immunostimulatory function in human renal cell carcinoma. / Lindner, Jonathan; Villanueva, Flordeliza S.; Dent, John M.; Wei, Kevin; Sklenar, Jiri; Kaul, Sanjiv.

In: Urological Research, Vol. 29, No. 5, 2001, p. 330-337.

Research output: Contribution to journalArticle

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