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Treatment Strategies in Metastatic Renal Cell Carcinoma

Cytokines, Vaccines, and Gene Therapy

  • Protocol
Renal Cancer

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 53))

Abstract

In recent years, the incidence of renal cell carcinoma (RCC) has increased dramatically (54% from 1975 to 1990), and in 1996, approx 30,000 new cases were diagnosed in the United States (1). In the same year, an estimated 12,000 RCC-related deaths occurred in the United States. The increased incidence of RCC in recent years may be linked to certain risk factors such as smoking, obesity, high-protein diets, and hypertension (2).

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References

  1. Parker, S. L., Tong, T., Bolden, S., and Wingo, P. A. (1996) Cancer Statistics CA Cancer J.65, 5–7.

    Google Scholar 

  2. Chow, W. H. and Gridley, G. (1994) Protein intake and risk of renal cell cancer. J. Natl. Cancer Inst.96, 1131–1139.

    Google Scholar 

  3. Golimbu, M., and Joshi, P. (1986) RCC: survival and prognostic factors. Urology27, 291–301.

    CAS  PubMed  Google Scholar 

  4. deKernion, J. B., Ramming, K., and Smith, R. (1978) The natural history of metastatic renal cell carcinoma: a computer analysis. J. Urol.120, 148–152.

    CAS  PubMed  Google Scholar 

  5. Franklin, J., Dorey, F., Gitlitz, B., and Belldegrun, A. (1996) Cytoreductive nephrectomy in 63 consecutaive patients who received adoptive immunotherapy for advanced RCC. J. Urol.155, 500A.

    Google Scholar 

  6. Kakehi, Y., Kanamaru, H., Yoshida, O., Ohkubo, H., Nakanishi, S., Gottesman, M., and Pastan, I. (1988) Measurement of multi-drug resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrisic drug resistance. J. Urol.139, 862–865.

    CAS  PubMed  Google Scholar 

  7. Fyfe, G., Fisher, R. I., Rosenberg, S. A., Sznol, M., Parkinson, D. R., and Louie, A. C. (1995) Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J. Clin. Oncol.13, 688–696.

    CAS  PubMed  Google Scholar 

  8. Fyfe, G. A., Fisher, R. I., Rosenberg, S. A., Sznol, M., Parkinson, D. R., and Louie, A. C. (1996) Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy. J. Clin. Oncol.14, 2410–2411.

    CAS  PubMed  Google Scholar 

  9. Yang, J. C., Topalian, S. L., Parkinson, D., Schwartzentruber, D. J., Weber, J. S., Ettinghausen, S. E., White, D. E., Steinberg, S. M., Cole, D. J., Kim, H. I., Levin, R., Guleria, A., MacFarlande, M. P., White, R. L., Einhorn, J. H., Seipp, C. A., and Rosenberg, S. A. (1994) Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J. Clin. Oncol.12, 1572–1576.

    CAS  PubMed  Google Scholar 

  10. Bennett, R. T., Lerner, S. E., Taub, H. C., Dutcher, J. P., and Fleischmann, J. (1995) Cytoreductive surgery for stage IV renal cell carcinoma. J. Urol.154, 32–34.

    CAS  PubMed  Google Scholar 

  11. Wirth, M. P. (1993) Immunotherapy for metastatic renal cell carcinoma. Urol. Clin. N. Am.20, 283–295.

    CAS  Google Scholar 

  12. Motzer, R. J., Schwartz, L., Law, T. M., Murphy, B. A., Hoffman, A. D., Albino, A. P., Vlamis, V., and Nanus, D. M. (1995) Interferon α-2a and 13-cis-retinoic acid in renal cell carcinoma: antitumor activity in a Phase II trial and interactions in vitro. J. Clin. Oncol.13, 1950–1957.

    CAS  PubMed  Google Scholar 

  13. Sarna, G., Figlin, R., and deKernion, J. B. (1987) Interferon in renal cell carcinoma. Cancer (Phila.)59, 610–612.

    CAS  Google Scholar 

  14. Chikkala, N. F., Lewis, I. Ulchaker, J. Stanley, J. Tubbs, R., and Finke, J. H. (1990) Interactive effects of α-interferon A/D and interleukin 2 on murine lymphokine-activated killer activity: analysis at the effector and precursor level. Cancer Res.50, 1176–1182.

    CAS  PubMed  Google Scholar 

  15. Sella, A., Kilbourn, R. G., Gray, I., Finn, L., Zukiwski, A. A., Ellerhorst, J., Amato, R. J., and Logothetis, C. J. (1994) Phase I study of interleukin-2 combined with interferon-α and 5-fluorouracil in patients with metastatic renal cell cancer. Cancer Biother.9, 103–111.

    CAS  PubMed  Google Scholar 

  16. Atzpodien, J., Kirchner, H., Hanninen, E. L., Deckert, M., Fenner, M., and Poliwoda, H. (1993) Interleukin-2 in combination with interferon-α and 5-fluorouracil for metastatic renal cell cancer. Eur. J. Cancer (29ASuppl. 5), S6–S8.

    PubMed  Google Scholar 

  17. Lopez Hanninen, E., Kirchner, H., and Atzpodien, J. (1996) Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J. Urol.155, 19–25.

    CAS  PubMed  Google Scholar 

  18. Wigginton, J. M., Kuhns, D. B., Back, T. C., Brunda, M. J., Wiltrout, R. H., and Cox, G. W. (1996) Interleukin 12 primes macrophages for nitric oxide production in vivo and restores depressed nitric oxide production by macrophages from tumor-bearing mice: implications for the antitumor activity of interleukin 12 and/or interleukin 2. Cancer Res.56, 1131–1136.

    CAS  PubMed  Google Scholar 

  19. Motzer, R. J., Rakhit, A., Schwartz, L. H., Olencki, T., Malone, T. M., Sandstrom, K., Nadeau, R., Parmar, H., and Bukowski, R. (1998) Phase I trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma. Clin Cancer Res.4, 1183–1191.

    CAS  PubMed  Google Scholar 

  20. Bukowski, R. M., Sharfman, W., Murthy, S., Rayman, P., Tubbs, R., Alexander, J., Budd, G. T., Sergi, J. S., Bauer, L., Gibson, V., Stanley, J. Boyett, J., Pontes, E., and Finke, J. (1991) Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. Cancer Res.51, 4199–4205.

    CAS  PubMed  Google Scholar 

  21. Figlin, R., Pierce, W. C., Kaboo, R., Tso, C. L., Moldawer, N., Dolan, N., Gitlitz, B., deKernion, J. B., and Belldegrun, A. (1997) Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+)-se-lected tumor-infiltrating lymphocytes from primary tumor. Urol. Sept; (1583 Pt 1), 740–745.

    CAS  Google Scholar 

  22. Gitlitz, B. J., Belldegrun, A., and Figlin, R. A. (1996) Immunotherapy and gene therapy. Semin. Urol. Oncol.14, 237–243.

    CAS  PubMed  Google Scholar 

  23. Graham, S., Babayan, R. K., Lamm, D. L., Sawczuk, I., Ross, S. D., Lavin, P. T., Osband, M. E., and Krane, R. J. (1993) The use of ex vivo-activated memory T cells autolymphocyte therapy) in the treatment of metastatic renal cell carcinoma: final results from a randomized, controlled, multisite study. Semin. Urol.11, 27–34.

    CAS  PubMed  Google Scholar 

  24. Pierce, W. C., Belldegrun, A., and Figlin, R. A. (1995) Cellular therapy: scientific rationale and clinical results in the treatment of metastatic renal cell carcinoma. Semin. Oncol.22, 74–80.

    CAS  PubMed  Google Scholar 

  25. Chang, A. E., Aruga, A., Cameron, M. J. Sondak, V. K. Normolle, D. P., Fox, B. A., and Shu, S. (1997) Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J. Clin. Oncol.15, 796–807.

    CAS  PubMed  Google Scholar 

  26. Steinman, R. M. (1991) The dendritic cell system and its role in immunogenicity. Ann. Rev. Immunol.9, 271–296.

    CAS  Google Scholar 

  27. Romani, N., Gruner, S., Brang, D., Kampgen, E., Lenz, A., Trockenbacher, B., Konwalinka, G., Fritsch, P. O., Steinman, R. M., and Schuler, G. (1994) Proliferating dendritic cell progenitors in human blood. J. Exp. Med.180, 83–93.

    CAS  PubMed  Google Scholar 

  28. Celluzi, C. M., Mayordomo, J. I., Storkus, W. J., Lotze, M. T., and Falo, L. D. (1996) Peptide-pulsed dendritic cells induce antigen-specific, CTL mediated protective tumor immunity. J. Exp. Med.183, 283–287.

    Google Scholar 

  29. Hsu, F. J., Benike, C., Fagnoni, F., Liles, T. M., Czerwinski, D., Taidi, B., Engleman, E. G., and Levy, R. (1996) Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat. Med.2, 52–58.

    CAS  PubMed  Google Scholar 

  30. Mukherji, B., Chakraborty, N. G., Yamasaki, S., Okino, T., Yamase, H., Sporn, J. R., Kurtzman, S. K., Ergin, M. T., Ozols, J., Meehan, J., et al. (1995) Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc. Natl. Acad. Sci. USA92, 8078–8082.

    CAS  PubMed  Google Scholar 

  31. Murphy, G., Tjoa, B., Ragde, H., Kenny, G., and Boynton, A. (1996) Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate29, 371–380.

    CAS  PubMed  Google Scholar 

  32. O′Sullivan, G. C., Corbett, A. R., Shanahan, F., and Collins, J. K. (1996) Regional immunosuppression in esophageal squamous cancer: evidence from functional studies with matched lymph nodes. J. Immunol.157, 4717–4720.

    PubMed  Google Scholar 

  33. Young, M. R., Wright, M. A., Lozano, Y., Matthews, J. P., Benefield, J., and Prechel, M. M. (1996) Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. Intl. J. Cancer67, 333–338.

    CAS  Google Scholar 

  34. Gabrilovich, D. I., Corak, J., Ciernek, I. F., Kavanaugh, D., and Carbone, D. P. (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin. Cancer Res.3, 483–490.

    CAS  PubMed  Google Scholar 

  35. Melief, C. J. (1989) Dendritic cells as specialized antigen-presenting cells. Res. Immunol.140, 902–907.

    CAS  PubMed  Google Scholar 

  36. Thurnher, M., Radmayr, C., Ramoner, R., Ebner, S., Bock. G., Klocker, H., Romani, N., and Bartsch, G. (1996) Human renal-cell carcinoma tissue contains dendritic cells. Intl. J. Cancer68, 1–7.

    CAS  Google Scholar 

  37. Bonham, C. A., Lu, L., Banas, R. A., Fontes, P., Rao, A. S., Starzl, T. E., Zeevi, A., and Thomson, A. W. (1996) TGF-β 1 pretreatment impaires the allostimula-tory function of human bone marrow-derived antigen-presenting cells for both naive and primed T cells. Transpl. Immunol.4, 186–191.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Chaux, P., Moutet, M., Faivre, J., Martin, F., and Martin, M. (1996) Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7–1 and B7–2 costimulatory molecules of the T-cell activation. Lab. Invest.74, 975–983.

    CAS  PubMed  Google Scholar 

  39. Gabrilovich, D. I., Chen, H. L., Girgis, K. R., Cunningham, H. T., Meny, G. M., Nadaf, S., Kavanaugh, D., and Carbone, D. P. (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med.2, 1096–103.

    CAS  PubMed  Google Scholar 

  40. Zied, N. A. and Muller, H. K. (1993) S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology25, 338–343.

    Google Scholar 

  41. Becker, Y. (1992) Anticancer role of dendritic cells (DC) in human and experimental cancers—a review. Anticancer Res.12, 511–520.

    CAS  PubMed  Google Scholar 

  42. Slingluff, C. L., Jr. (1996) Tumor antigens and tumor vaccines: peptides as immu-nogens. Semin. Surg. Oncol.12, 446–453.

    PubMed  Google Scholar 

  43. Mayordomo, J. I., Zorina, T., Storkus, W. J., Zitvogel, L., Garcia-Prats, M. D., DeLeo, A. B., and Lotze, M. T. (1997) Bone marrow-derived dendritic cells serve as potent adjuvants for peptide-based antitumor vaccines. Stem Cells15, 94–103.

    CAS  PubMed  Google Scholar 

  44. Porgador, A., Snyder, D., and Gilboa, E. (1996) Induction of antitumor immunity using bone marrow-generated dendritic cells. J. Immunol.156, 2918–2926.

    CAS  PubMed  Google Scholar 

  45. Tjoa, B., Boynton, A., Kenny, G., Ragde, H., Misrock, S. L., and Murphy, G. (1996) Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity. Prostate28, 65–69.

    CAS  PubMed  Google Scholar 

  46. Cohen, P. A., Cohen, P. J., Rosenberg, S. A., and Mule, J. J. (1994) CD4+ T-cells from mice immunized to syngeneic sarcomas recognize distinct, non-shared tumor antigens. Cancer Res.54, 1055–1058.

    CAS  PubMed  Google Scholar 

  47. Zitvogel, L., Mayordomo, J. I., Tjandrawan, T., DeLeo, A. B., Clarke, M. R., Lotze, M. T., and Storkus, W. J. (1996) Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J. Exp. Med.183, 87–97.

    CAS  PubMed  Google Scholar 

  48. Sahin, U., Tureci, O., Schmitt, H., Cochlovius, B., Johannes, T., Schmits, R., Stenner, F., Luo, G., Schobert, I., and Pfreundschuh, M. (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proc. Natl. Acad. Sci. USA92, 11810–11813.

    CAS  PubMed  Google Scholar 

  49. Koch, F., Stanzl, U., Jennewein, P., Janke, K., Heufler, C., Kampgen, E., Romani, N., and Schuler, G. (1996) High level IL-12 production by murine dendritic cells:upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J. Exp. Med.184, 741–746.

    CAS  PubMed  Google Scholar 

  50. Cella, M., Scheidegger, D., Palmer-Lehmann, K., Lane, P., Lanzavecchia, A., and Alber, G. (1996) Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med.184, 747–752.

    CAS  PubMed  Google Scholar 

  51. Zeh, H. J., 3d., Hurd, S., Storkus, W. J., and Lotze, M. T. (1993) Interleukin-12 promotes the proliferation and cytolytic maturation of immune effectors: implications for the immunotherapy of cancer. J. Immunoth.14, 155–161.

    CAS  Google Scholar 

  52. Romani, N., Reider, D., Heuer, M., Ebner, S., Kampgen, E., Eibl, B., Nieder-wieser, D., and Schuler, G. (1993) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J. Immunol. Methods196, 137–151.

    Google Scholar 

  53. Bender, A., Sapp, M., Schuler, G., Steinman, R. M., and Bhardwaj, N. (1996) Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. J. Immunol. Methods196, 121–135.

    CAS  PubMed  Google Scholar 

  54. Golumbek, P., Levitsky, H., Jaffee, L. and Pardoll, D. M. (1993) The antitumor immune response as a problem of self-nonself discrimination: implications for immunotherapy. Immunol. Res.12, 183–192.

    CAS  PubMed  Google Scholar 

  55. Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K., Jack-son, V., Hamada, H., Pardoll, D., and Mulligan, R. C. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc. Natl. Acad. Sci. USA90, 3539–3543.

    CAS  PubMed  Google Scholar 

  56. Jaffee, E. M., Marshall, F., Weber, C., Pardoll, D. M., Levitsky, H., Nelson, W., Carducci, M., Mulligan, R., and Simons, J. (1996) Bioactivity of a human GM-CSF tumor vaccine for the treatment of metastatic renal cell carcinoma. Proc. Am. Soc. Clin. Oncol.15, 237.

    Google Scholar 

  57. Sun, W. H., Burkholder, J. K., Sun, J., Culp, J., Turner, J., Lu, X. G., Pugh, T. D., Ershler, W. B., and Yang, N. S. (1995) In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc. Natl. Acad. Sci. USA92, 2889–2893.

    CAS  PubMed  Google Scholar 

  58. Nabel, G. J., Yang, Z. Y., Nabel, E. G., Bishop, K., Marquet, M., Felgner, P. L., Gordon, D., and Chang, A. E. (1995) Direct gene transfer for treatment of human cancer. Ann. NY Acad. Sci.772, 227–231.

    CAS  PubMed  Google Scholar 

  59. Vogelzang, N. J., Lestingi, T. M., Sudakoff, G., and Kradjian, S. A. (1994) Phase I study of immunotherapy of metastatic renal cell carcinoma by direct gene transfer into metastatic lesions. Hum. Gene Ther.5, 1357–1370.

    CAS  PubMed  Google Scholar 

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Mulders, P.F. (2001). Treatment Strategies in Metastatic Renal Cell Carcinoma. In: Mydlo, J.H. (eds) Renal Cancer. Methods in Molecular Medicine, vol 53. Humana, Totowa, NJ. https://doi.org/10.1385/1-59259-144-2:343

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  • DOI: https://doi.org/10.1385/1-59259-144-2:343

  • Publisher Name: Humana, Totowa, NJ

  • Print ISBN: 978-0-89603-828-8

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