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Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study

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Abstract

Purpose

Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (γδ) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated γδ T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study.

Experimental design

Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous γδ T cells every week or every 2 weeks, 6–12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and immunomonitoring was performed by flow cytometric analysis.

Results

Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients; these three patients showed an increase in the number of γδ T cells in peripheral blood and also a high response to the antigen in vitro.

Conclusions

The results indicated that adoptive immunotherapy using in vitro-activated autologous γδ T cells was well tolerated and induced anti-tumor effects.

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References

  1. de Rise W, Allhoff E, Kirchner H, Stief CG, Atzpodien J, Maschek H, Jonas U (1991) Complete spontaneous regression in metastatic renal cell carcinoma—an update and review. World J Urol 9:1841–1843

    Google Scholar 

  2. Dekernion JB, Ramming KP, Smith RB (1978) The natural history of metastatic renal cell carcinoma, A computer analysis. J Urol 120:148–152

    PubMed  CAS  Google Scholar 

  3. Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271:907–913

    Article  PubMed  CAS  Google Scholar 

  4. Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T (1988) Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 338:1272–1278

    Article  Google Scholar 

  5. Aulitzky W, Gastl G, Aulitzky WE, Herold M, Kemmler J, Mull B, Frick J, Huber C (1989) Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma. J Clin Oncl 7:1875–1884

    CAS  Google Scholar 

  6. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seioo CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492

    Article  PubMed  CAS  Google Scholar 

  7. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316:889–897

    Article  PubMed  CAS  Google Scholar 

  8. Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233:1318–1321

    Article  PubMed  CAS  Google Scholar 

  9. Hayakawa K, Salmeron MA, Parkinson DR, Morkowitz AB, von Eschenbach AC, Legha SS, Balch CM, Ross MI, Augustus LB, Ito K (1991) Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC. J Immunother 10:313–325

    Article  PubMed  CAS  Google Scholar 

  10. Figlin RA, Thompson JA, Bukowski RM et al (1999) Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol 17:2521–2529

    PubMed  CAS  Google Scholar 

  11. Holtl L. Zelle-Rieser C, Gander H et al (2002) Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8:3369–3376

    Google Scholar 

  12. Childs R, Chernoff A, Contentin N et al (2000) Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 343(11):750–758

    Article  PubMed  CAS  Google Scholar 

  13. Porcelli S, Brenner MB, Band H (1991) Biology of human γδ-T cell receptor. Immunol Rev 120:137–183

    Article  PubMed  CAS  Google Scholar 

  14. Constant P, Davodeau F, Peyrat MA, Poquet Y, Puzo G, Bonneville M, Fournié JJ (1994) Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands. Science 264:267–270

    Article  PubMed  CAS  Google Scholar 

  15. Tanaka Y, Morita CT, Tanaka Y, Nieves E, Brenner MB, Bloom BR (1995) Natural and synthetic nonpeptide antigens recognized by human γδ T cells. Nature 375:155–158

    Article  PubMed  CAS  Google Scholar 

  16. Bukowski JF, Morita CT, Brenner MB (1999) Human gamma delta T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity 11:57–65

    Article  PubMed  CAS  Google Scholar 

  17. Kobayashi H, Tanaka Y, Yagi J et al (2001) Gamma/delta T cells provide innate immunity against renal cell carcinoma. Cancer Immunol Immunother 50:115–124

    Article  PubMed  CAS  Google Scholar 

  18. Kabelitz D, Wesch D, Pitters E et al (2004) Characterization of tumor reactivity of human Vγ9Vδ2 γδ T cells in vitro and in SCID mice in vivo. J Immunol 173:6767–6776

    PubMed  CAS  Google Scholar 

  19. Wilhelm M, Kuzmann Y, Eckstein S et al (2003) γδ T cells for immune therapy of patients with lymphoid malignancies. Blood 102:200–206

    Article  PubMed  CAS  Google Scholar 

  20. Takahashi N, Imanishi K, Nishida H et al (1995) Evidence for immunologic immaturity of cord blood T cells, cord blood T cells are susceptible to tolerance induction to in vitro stimulation with a superantigen. J Immunol 155:5213–5219

    PubMed  CAS  Google Scholar 

  21. Ozono S, Miyano N, Igarashi T et al (2004) Tumor doubling time of renal cell carcinoma measured by CT: collaboration group of Japanese Society of Renal Cancer. Jpn J Clin Oncol 34:82–85

    Article  PubMed  Google Scholar 

  22. Kudo D, Rayman P, Horton C et al (2003) Gangliosides expressed by the renal cell carcinoma cell line SK-RC-45 are involved in tumor-induced apoptosis of T cells. Cancer Res 63:1676–1683

    PubMed  CAS  Google Scholar 

  23. Brandes M, Willimann K, Moser B (2005) Professional antigen-presentation function by human gamma delta T cells. Science 309:264–268

    Article  PubMed  CAS  Google Scholar 

  24. Kato Y, Tanaka Y, Tanaka H, Yamashita S, Minato N (2003) Requirement of species-specific interactions for the activation of human gamma delta T cells by pamidronate. J Immunol 170:3608–3613

    PubMed  CAS  Google Scholar 

  25. Kabelitz D, Wesch D, Pitters E, Zoller M (2004) Characterization of tumor reactivity of human V gamma 9V delta 2 gamma delta T cells in vitro and in SCID mice in vivo. J Immunol 173:6767–6776

    PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Ms Barbara Levene for reviewing our paper before submission, and Dr. Fumio Ito, Dr. Tunenori Kondo and Dr. Yasunobu Hashimoto for providing us with samples. This research was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan and the Ministry of Health and Welfare of Japan.

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Correspondence to Hirohito Kobayashi.

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Kobayashi, H., Tanaka, Y., Yagi, J. et al. Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study. Cancer Immunol Immunother 56, 469–476 (2007). https://doi.org/10.1007/s00262-006-0199-6

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  • DOI: https://doi.org/10.1007/s00262-006-0199-6

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