Interleukin-2 in Renal Cell Carcinoma: A Has-Been or a Still-Viable Option?
Main Article Content
Keywords
IL-2, interleukin-2, immunomodulation, immunotherapy, renal cell carcinoma
Abstract
Modulation of the immune response plays an important role in the natural history of renal cell carcinoma. Spontaneous regression of metastases has been well documented in a small percentage of patients after they undergo de-bulking nephrectomy without any additional systemic intervention. The only logical explanation for these observations is “resetting” of the balance between tumor and the host immune system that, having been overwhelmed by the tumor burden, is able to function better after tumor de-bulking. Attempts to modulate the activity of the immune system “on demand” have included the use of vaccines, cytokines/lymphokines, adoptive cell transfer, monoclonal antibodies and most recently manipulation of immune checkpoint inhibitors. Here we review the data for infusional interleukin-2 in the management of advanced renal cell carcinoma and its role in current clinical practice.
References
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39. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA 4 blockade. Science 1996;271:1734-6. Doi: http://dx.doi.org/10.1126/science.271.5256.1734
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2. Oliver RTD, Nethersell AB, Bottomly JM. Unexplained spontaneous regression and alpha interferon as treatment for metastatic renal cell carcinoma. Br J Urol. 1989; 63:128-131. [PMid: 2702395]
3. Vogelzang NJ, Priest ER, Borden L. Spontaneous regression of histologically proved pulmonary metastases from renal cell carcinoma: a case with 5-year followup. J Urol. 1992;148:1247-8. [PMid:1404646].
4. Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976;193:1007-8. Doi: http://dx.doi.org/10.1126/science.181845.
5. Gillis S, Smith KA. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977;268:154-6. Doi: http://dx.doi.org/10.1038/268154a0
6. Gillis S, Ferm M, Ou W, Smith KA. T cell growth factor: Parameters of production and a quantitative micro-assay for activity. J Immunol. 1978;120:2027-2032. [PMid:307029].
7. Second International Lymphokine Workshop held in Ermatingen, Switzerland 1979.
8. Lotze M, Grimm E, Mazumder A et al. Lysis of fresh and cultured autologous tumor by lymphocytes cultured in T cell growth factor. Cancer Res. 1981;41:4420. [PMid:6975652].
9. Grimm E, Mazumder A, Zhang Z et al. The ymphokine activated killer cell phenomena. Lysis of natural killer-resistant fresh solid tumor cells by interleukin-2 activated autologous human peripheral blood lymphocytes. J Exp Med. 1982;155:1823. Doi: http://dx.doi.org/10.1084/jem.155.6.1823. PMid:6176669
10. Mazumder A, Rosenberg SA. Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin-2. J Exp Med. 1984;159:495. Doi: http://dx.doi.org/10.1084/jem.159.2.495
11. Mule J, Shu S, Schwarz S, Rosenberg SA. Successful adoptive immunotherapy of established pulmonary metastasis of multiple sarcomas with lymphokine activated killer cells and recombinant interleukin-2. Science (Wash DC) 1984;225:1487. Doi: http://dx.doi.org/10.1126/science.6332379
12. Ettinghausen S, Lipford E, Mule J, Rosenberg SA. Recombinant interleukin-2 stimulates in vivo proliferation of adoptively transferred lymphokine activated killer cells. J Immunol. 1985;135:3623-35. [PMid:3900213].
13. Rosenberg SA, Mule J, Spiess P et al. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin-2. J Exp Med. 1985;1169-1188. Doi: http://dx.doi.org/10.1084/jem.161.5.1169
14. Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature. 1983;302:305-10. Doi: http://dx.doi.org/10.1038/302305a0
15. Rosenberg SA, Lotze MT, Muul L et al. Observations on the systemic administration of autologous lymphokine activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313:1485. Doi: http://dx.doi.org/10.1056/NEJM198512053132327
16. Smith KA. Interleukin-2: Inception, impact, and implications. Science. 1988;240:1169-76. Doi: http://dx.doi.org/10.1126/science.3131876
17. Rosenberg SA, Lotze MT, Muul LM et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and IL-2 or high-dose interleukin-2 alone. N Engl J Med. 1987;316:889-897. Doi: http://dx.doi.org/10.1056/NEJM198704093161501
18. Rosenberg SA, Yang JC, Topalian SL et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2. JAMA. 1994;271;907-913. Doi: http://dx.doi.org/10.1001/jama.1994.03510360033032
19. Fyfe G, Fisher RI, Rosenberg SA et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13:688-696. [PMid:7884429].
20. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival after high-dose recombinant interleukin-2 in patients with renal cell carcinoma. The Cancer Journal from Scientific American. 2000, 6 Suppl 1:S55-7. [PMid:10685660].
21. Klapper JA, Downey SG, Smith FO et al. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma. Cancer. 2008;113:293. Doi: http://dx.doi.org/10.1002/cncr.23552
22. McDermott DF, Ghebremichael MS, Signoretti S et al. The high-dose IL-2 "SELECT" trial in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010;28:345s.
23. Negrier S, Escudier B, Lasset C et al. Recombinant human interleukin-2, recombinant human interferon alpha 2a or both in metastatic renal cell carcinoma. N Engl J Med. 1998;338:1272-1278. Doi: http://dx.doi.org/10.1056/NEJM199804303381805
24. Yang JC, Sherry RM, Steinberg SM et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003;21:3127-3132. Doi: http://dx.doi.org/10.1200/JCO.2003.02.122
25. McDermott, DF, Regan MM, Clark JI et al. Randomized phase 3 trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005;23:133-141. Doi: http://dx.doi.org/10.1200/JCO.2005.03.206
26. Negrier S, Perol D, Ravaud A et al. Medroxyprogesterone, interferon alpha 2a, interleukin-2 or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis. Cancer. 2007;110:2468-2477. Doi: http://dx.doi.org/10.1002/cncr.23056
27. Schwartzentruber D J. Guidelines for the safe administration of high-dose interleukin-2. J Immunother. 2001;24:287-293. Doi: http://dx.doi.org/10.1097/00002371-200107000-00004
28. Amin A, White RL. High-Dose Interleukin-2: Is it still indicated for Melanoma and RCC in an Era of Targeted Therapies? Oncology 2013; (27)7: 680-91. [PMid: 23977763].
29. Hanzly M, Aboumohamed A, Yarlagadda N et al. High-dose interleukin therapy for metastatic renal cell carcinoma: A contemporary experience. Urology 2014;83:1129-1134. Doi: http://dx.doi.org/10.1016/j.urology.2014.02.005
30. Payne R, Glenn L, Hoen H et al. Durable responses in reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cell cancer in a community Hospital biotherapy program. J Immunother of Cancer 2014;2:13. Doi: http://dx.doi.org/10.1186/2051-1426-2-13
31. Kauffman HL, Wong MK, Daniels GA et al. The use of registries to improve cancer treatment: National database for patients treated with interleukin-2. J Pers Med. 2014;4:52-64. Doi: http://dx.doi.org/10.3390/jpm4010052
32. Cho DC, Puzanov I, Regan MM et al. Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J Immunother. 2009;32:181-185. Doi: http://dx.doi.org/10.1097/CJI.0b013e3181952b1d
33. Morse M, McDermott D, Daniels, G et al. High-dose IL-2 for metastatic renal cell carcinoma in the targeted therapy era: Extension of overall survival benefits beyond complete response and partial response. J Clin Oncol. 2014;32:5s (suppl; abstr 4523).
34. FDA approved drugs [internet].
35. Heng DY, Xie W, Regan MM et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor targeted agents: Results from a large multicenter study. J Clin Oncol. 2009;27:5794. Doi: http://dx.doi.org/10.1200/JCO.2008.21.4809
36. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64. Doi: http://dx.doi.org/10.1038/nrc3239
37. Topalian SL, Weiner Gj, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol 2011;29:4828-36. Doi: http://dx.doi.org/10.1200/JCO.2011.38.0899
38. Motzer RJ, Rini BI, McDermott DF et al. Nivolumab for metastatic renal cell carcinoma: Results of a randomized dose ranging phase II trial. J Clin Oncol 32:5s, 2014 (suppl:abstr 5009).
39. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA 4 blockade. Science 1996;271:1734-6. Doi: http://dx.doi.org/10.1126/science.271.5256.1734
40. Hammers H, Plimack E, Infante JR et al. Phase I study of Nivolumab in combination with Ipilimumab in metastatic renal cell carcinoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 4504).
41. Amin A, Plimack E, Infante JR et al. Nivolumab in combination with sunitinib or pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 5010).
42. NCCN Kidney Cancer Guidelines Version 1.2015 accessed October 27, 2014 http://www.nccn.org/
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Nov 23, 2014
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Interleukin-2 in Renal Cell Carcinoma: A Has-Been or a Still-Viable Option?. (2014). Journal of Kidney Cancer and VHL, 1(7), 74-83. https://doi.org/10.15586/jkcvhl.2014.18
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Kidney Cancer: Review Articles
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