Advertisement

Prediction of Cytokine-Therapy on Basis of Class-I and Class-II MHC Antigen Induction

  • A. J. M. C. Beniers
  • W. P. Peelen
  • F. M. J. Debruyne
  • J. A. Schalken
Conference paper

Abstract

Cytokine therapy has proven to be effective in approximately 15% of the patients with metastatic renal cell carcinoma (RCC). In the further implementation of this still experimental therapeutic modality, two questions are considered relevant, i.e., how can the optimal cytokine treatment combination and dosage be determined, and are there markers predicting a response. Recent findings indicate that the optimal doses can vary for individual patients [2]. Moreover, insight into the best combination of cytokines is not yet available. In the identification of patients that respond to immunotherapy, both host mediated effects as well as tumor cell characteristics should be considered. In this study special emphasis was given to the role of histocompatibility antigens as a predictor for response. These molecules play an important role in both the presentation of autologous and or heterologous antigens to the immune system and result in eventual binding and elimination. Furthermore, it has been recognized that these molecules can be induced by several cytokines. In a previous study in which we studied the cytokine sensitivity of eight human RCC xenografts in a nude mouse model we found a variable response to the treatment with interferon-alpha, — gamme and tumor necrosis factor (TNF) [4]. In the same model we evaluated the level of expression of histocompatibility leucocyte antigens (HLA) and the modulation by cytokines. The nude mouse model does not permit conclusions regarding the functional role of these molecules in an eventual host mediated response induced by immunotherapy; however, the expression and inducibility of HLA class-I and class-II molecules can be correlated with the nonimmune mediated antitumor response.

Keywords

Renal Cell Carcinoma Metastatic Renal Cell Carcinoma Tumor Line Nude Mouse Model Cytokine Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Auffray C, Rougeon W (1980) Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem 107: 303–314PubMedCrossRefGoogle Scholar
  2. 2.
    Aulitzky W, Gastl G, Aulitzky WE, et al. (1990) Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma. J Clin Oncol 7: 1875–1884Google Scholar
  3. 3.
    Barnstable CJ, Bodmer WF, Brown G, Galfre G, Milstein C, Williams AF, Ziegler A (1978) Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens- New tools for genetic analysis. Cell 14: 9–20PubMedCrossRefGoogle Scholar
  4. 4.
    Beniers AJMC, van Moorselaar RJA, Peelen WP, Debruyne FMJ, Schalken JA (1991) Differential sensitivity of renal cell carcinoma xeno-grafts towards therapy with interferon-alpha, interferon-gamma, tumor necrosis factor and their combinations. Urol Res 19: 91–98PubMedCrossRefGoogle Scholar
  5. 5.
    Beniers AJMC, Peelen WP, Schaafsma HE, Beck JLM, Debruyne FMJ, Schalken JA (1991) Establishment and characterization of five new renal tumor xenografts. Am J Path (in press )Google Scholar
  6. 6.
    Höehn W, Schroeder FH (1978) Renal cell carcinoma: two new cell lines and a serially transplantable nude mouse tumor (NC-65). Invest Urol 16: 106–112PubMedGoogle Scholar
  7. 7.
    Lemonnier FA, Rebai N, le Bouteiller PP, Malissen B, Caillol DH, Kourilsky FM (1982) Epitopic analysis of detergent-solubilized HLA molecules by solid-phase radioimmunoassay. J Immunol Methods 54: 9–22PubMedCrossRefGoogle Scholar
  8. 8.
    Rubin JT, Elwood LJ, Rosenberg SA, Lotze MT (1989) Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. Cancer Res 49: 7086–7092PubMedGoogle Scholar
  9. 9.
    Seakaly RP, Tonnelle C, Strubin M, Mach. B, Long EO (1986) Cell surface expression of class II histocompatibility antigens occur in the absence of the invariant chain. J Exp Med 164: 1490–1504CrossRefGoogle Scholar
  10. 10.
    Sood AK, Pereira D, Weissman SM (1981) Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci USA 78: 616–620PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • A. J. M. C. Beniers
  • W. P. Peelen
  • F. M. J. Debruyne
  • J. A. Schalken
    • 1
  1. 1.Urologie Research Laboratory, Department of UrologyUniversity Hospital NijmegenNijmegenThe Netherlands

Personalised recommendations