Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: Ability to maintain IFN-γ induction is associated with clinical response

Clinical Cancer Research

Volumn 6, Issue 5, 2000, Pages 1678-1692

  Gollob, Jared A ^a   Mier, James W ^a   Veenstra, Korina ^a   McDermott, David F ^a   Clancy, Daniel ^a   Clancy, Marguerite ^a   Atkins, Michael B ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 10; RECOMBINANT INTERLEUKIN 12;

ADULT; AGED; ARTICLE; CANCER IMMUNOTHERAPY; CLINICAL ARTICLE; CLINICAL TRIAL; CYTOKINE PRODUCTION; DOSE RESPONSE; DRUG RESPONSE; FEMALE; HUMAN; KIDNEY CARCINOMA; MALE; MELANOMA; METASTASIS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; TREATMENT OUTCOME;

ADULT; AGED; ARTHRALGIA; CARCINOMA, RENAL CELL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FEVER; HEMATOLOGIC DISEASES; HUMANS; HYPOTENSION; INJECTIONS, INTRAVENOUS; INTERFERON TYPE II; INTERLEUKIN-12; INTERLEUKIN-15; INTERLEUKIN-18; KIDNEY NEOPLASMS; MALE; MELANOMA; MIDDLE AGED; MOUTH MUCOSA; NEOPLASM METASTASIS; RECOMBINANT PROTEINS; SKIN; STOMATITIS; TIME FACTORS;

EID: 0034103809     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (46)

1. Kobayashi, M., Fitz, L., Ryan, M., Hewick, R., Clark, S., Chan, S., Loudon, R., Sherman, F., Perussia, B., and Trinchieri, G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J. Exp. Med., 170: 827-845, 1989.
2. Chan, S. H., Perussia, B., Gupta, J. W., Kobayashi, M., Pospisil, M., Young, H. A., Wolf, S. F., Young, D., Clark, S. C., and Trinchieri, G. Induction of interferon-γ production by natural killer cell stimulatory factor: characterization of responder cells and synergy with other inducers. J. Exp. Med., 173: 869-879, 1991.
3. Robertson, M. J., Soiffer, R. J., Wolf, S. F., Manley, T. J., Donahue, C., Young, D., Herrmann, S. H., and Ritz, J. Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells is differentially regulated by NKSF. J. Exp. Med., 175: 779-788, 1992.
4. Mehrotra, P. T., Wu, D., Crim, J. A., Mostowski, H. S., and Siegel, J. P. Effects of IL-12 on the generation of cytoloxic activity in human CD8+ T lymphocytes. J. Immunol., 151: 2444-2452, 1993.
5. Jelinek, D. F., and Braaten, J. K. Role of IL-12 in human B lymphocyte proliferation and differentiation. J. Immunol., 154: 1606-1613, 1995.
6. Grohmann, U., Belladonna, M. L., Bianchi, R., Orabona, C., Ayroldi, E., Fioretti, M. C., and Puccetti, P. IL-12 acts directly on DC to promote nuclear localization of NF-KB and primes DC for IL-12 production. Immunity, 9: 315-323, 1998.
7. 2+ and tyrosine signaling pathways in human neutrophils. J. Immunol., 161: 3737-3745, 1998.
8. Yeaman, G. R., Collins, J. E., Currie, J. K., Guyre, P. M., Wira, C. R., and Fanger, M. W. IFN-γ is produced by polymorphonuclear neutrophils in human uterine endometrium and by cultured peripheral blood polymorphonuclear neutrophils. J. Immunol., 160: 5145-5153, 1998.
9. Brunda, M. J., Luistro, L., Warrier, R. R., Wright, R. B., Hubbard, B. R., Murphy, M., Wolf, S. F., and Gately, M. K. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J. Exp. Med., 178: 1223-1230, 1993.
10. Nastala, C. L., Edington, H. D., McKinney, T. G., Tahara, H., Nalesnifc, M. A., Brunda, M. J., Gately, M. K., Wolf, S. F., Schreiber, R. D., Storkus, W. J., and Lotze, M. T. Recombinant IL-12 administration induces tumor regression in association with IFN-γ production. J. Immunol., 153: 1607-1706, 1994.
11. Cavallo, F., Di Carlo, E., Butera, M., Verrua, R., Colombo, M. P., Musiani, P., and Forni, G. Immune events associated with the cure of established tumors and spontaneous metastases by local and systemic interleukin 12. Cancer Res., 59: 414-421, 1999.
12. Cui, J., Shin, T., Kawano, T., Sato, H., Kondo, E., Toura, I., Kaneko, Y., Koseki, H., Kanno, M., and Taniguchi, M. Requirement for Vα14 NKT cells in IL-12-mediated rejection of tumors. Science (Washington DC), 278: 1623-1626, 1997.
13. Voest, E. E., Kenyon, B. M., O'Reilly, M. S., Truitt, G., D'Amato, R. J., and Folkman, J. Inhibition of angiogenesis in vivo by interleukin 12. J. Natl. Cancer Inst., 87: 581-586, 1995.
14. Gollob, J. A., Schnipper, C. P., Orsini, E., Murphy, E., Daley, J. F., Lazo, S. B., Frank, D. A., Neuberg, D., and Ritz, J. Characterization of a novel subset of CD8+ T cells that expands in patients receiving interleukin-12. J. Clin. Invest., 102: 561-575, 1998.
15. Carson, W. E., Giri, J. G., Lindemann, M. J., Linett, M. L., Ahdieh, M., Paxton, R., Anderson, D., Eisenmann, J., Grabstein, K., and Caligiuri, M. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J. Exp. Med., 180: 1395-1403, 1994.
16. Micallef, M. J., Ohtsuki, H., Kohno, K., Tanabe, F., Ushio, T., Namba, M., Tanimoto, T., Torigoe, K., Fuji, M., Ikeda, M., Fukuda, S., and Kurimoto, M. Interferon-γ-inducing factor enhances T helper 1 cytokine production by stimulating human T cells: synergism with interleukin-12 for interferon-γ production. Eur. J. Immunol., 26: 1647-1651, 1996.
17. Fantuzzi, G., Reed, D. A., and Dinarello, C. A. IL-12-induced IFN-γ is dependent on caspase-1 processing of the IL-18 precursor. J. Clin. Investig., 104: 761-767, 1999.
18. Atkins, M., Robertson, M., Gordon, M., Lotze, M., DeCoste, M., DuBois, J., Ritz, J., Sandler, A., Edington, H., Garzone, P., Mier, J., Canning, C., Battiatio, L., and Sherman, M. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin. Cancer Res., 3: 409-417, 1997.
19. Robertson, M. J., Cameron, C., Atkins, M. B., Gordon, M. S., Lotze, M. T., Sherman, M. L., and Ritz, J. Immunologic effects of interleukin 12 administered by bolus intravenous injection to patients with cancer. Clin. Cancer Res., 5: 9-16, 1999.
20. Bajetta, A., Vecchio, M. D., Mortarini, R., Nadeau, R., Rakhit, A., Rimassa, L., Fowst, C., Borri, A., Anichini, A., and Parmiani, G. Pilot study of subcutaneous recombinant human interleukin 12 in metastatic melanoma. Clin. Cancer Res., 4: 75-85, 1998.
21. Motzer, R. J., Rakhit, A., Schwartz, L. H., Olencki, T., Malone, T. M., Sandstrom, K., Nadeau, R., Parmar, H., and Bukowski, R. Phase I Trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma. Clin. Cancer Res., 4: 1183-1191, 1998.
22. Kruit, W. H. J., Schuler, M., Portielje, J. E. A., Beck, J., Lamers, C., Huber, C., Gratam, J. W., de Boer-Dennert, M., Rakhit, A., Aulitzky, W. E., Bolhuis, R. L. H., and Stoter, G. Phase I study of recombinant interleukin-12 subcutaneously in patients with advanced renal cell carcinoma. Proc. Am. Assoc. Cancer Res., 40: 574, 1999.
23. Leonard, J. P., Sherman, M. L., Fisher, G. L., Buchanan, L. J., Larsen, G., Atkins, M. B., Sosman, J. A., Dutcher, J. P., Vogelzang, N. J., and Ryan, J. L. Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-γ production. Blood, 90: 2541-2548, 1997.
24. Coughlin, C. M., Wysocka, M., Trinchieri, G., and Lee, W. M. F. The effect of interleukin 12 desensitization on the antitumor efficacy of recombinant interleukin 12. Cancer Res., 57: 2460-2467, 1997.
25. Kurzawa, H., Wysocka, M., Aruga, E., Chang, A. E., Trinchieri, G., and Lee, W. M. F. Recombinant interleukin 12 enhances cellular immune responses to vaccination only after a period of suppression. Cancer Res., 58: 491-499, 1998.
26. Koblish, H. K., Hunter, C. A., Wysocka, M., Trinchieri, G., and Lee, W. M. F. Immune suppression by recombinant interleukin (rIL)-12 involves interferon-γ induction of nitric oxide synthase 2 (iNOS) activity: inhibitors of NO generation reveal the extent of rIL-12 vaccine adjuvant effect. J. Exp. Med., 188: 1603-1610, 1998.
27. Gollob, J. A., Li, J., Reinherz, E. L., and Ritz, J. CD2 regulates responsiveness of activated T cells to interleukin 12. J. Exp. Med., 182: 721-731, 1995.
28. Atkins, M., Lotze, M., Dutcher, J., Fisher, R., Margolin, K., Weiss, G., Abrams, J., Sznol, M., Parkinson, D., Hawkins, M., Paradies, C., Kunkel, L., and Rosenberg, S. A. High-dose recombinant interleukin-2 therapy for metastatic melanoma: analysis of 270 patients treated from 1985-1993. J. Clin. Oncol., 17: 2105-2116, 1999.
29. Pluda, J. M. Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. Semin. Oncol., 24: 203-218, 1997.
30. Eisen, T., Boshoff, C., Mak, I., Pyle, L., Johnston, S., Ahern, R., Smith, I. E., and Gore, M. E. A phase II study of continuous low dose thalidomide in patients with renal cell, melanoma, ovarian, and breast cancer. J. Immunother., 22: 458, 1999.
31. D'Amato, R. J., Loughnan, M. S., Flynn, E., and Folkman, J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. USA, 91: 4082-4085, 1994.
32. Rook, A. H., Wood, G. S., Yoo, E. K., Elenitsas, R., Kao, D. M., Sherman, M. L., Witmer, W. K., Rockwell, K. A., Shane, R. B., Lessin, S. R., and Vonderheid, E. C. Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T cell responses. Blood, 94: 902-908, 1999.
33. Rosenberg, S. A., Yang, J. C., Topalian, S. L., Schwartzentruber, D. J., Weber, J. S., Parkinson, D. R., Seipp, C. A., Einhorn, J. H., and White, D. E. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. J. Am. Med. Assoc., 277; 907-913, 1994.
34. Eng, V. M., Car, B. D., Schnyder, B., Lorenz, M., Serena, L., Aguet, M., Anderson, T. D., Ryffel, B., and Quesniaux, V. F. The stimulatory effects of Interleukin (IL)-12 on hematopoiesis are antagonized by IL-12-induced interferon-γ in vivo. 1. Exp. Med., 181: 1893-1898, 1995.
35. Jonuleit, H., Wiedemann, K., Muller, G., Degwert, J., Hoppe, U., Knop, J., and Enk, A. H. Induction of IL-15 messenger RNA and protein in human blood-derived dendritic cells: a role for IL-15 in attraction of T cells. J. Immunol., 158: 2610-2615, 1997.
36. Stoll, S., Jonuleit, H., Schmitt, E., Muller, G., Yamauchi, H., Kurimoto, M., Knop, J., and Enk, A. H. Production of functional IL-18 by different subtypes of murine and human dendritic cells (DC): DC-derived IL-18 enhances IL-12-dependent Th1 development. Eur. J. Immunol., 28: 3231-3239, 1998.
37. Carson, W. E., Ross, M. E., Baiocchi, R. A., Marien, M. J., Boiani, N., Grabstein, K., and Caligiuri, M. A. Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-γ by natural killer cells in vitro. J. Clin. Invest., 96: 2578-2582, 1995.
38. Musso, T., Calosso, L., Zucca, M., Millesimo, M., Ravarino, D., Giovarelli, M., Malavasi, F., Ponzi, A. N., Paus, R., and Bulfone-Paus, S. Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma upregulated interleukin-15. Blood, 93: 3531-3539, 1999.
39. Novick, D., Kim, S-H., Fantuzzi, G., Reznikov, L. L., Dinarello, C. A., and Rubinstein, M. Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity, 10: 127-136, 1999.
40. Johnston, J. A., Bacon, C. M., Riedy, M. C., and O'Shea, J. J. Signaling by IL-2 and related cytokines: JAKs, STATs, and relationship to immunodeficiency. J. Leukocyte Biol., 60: 441-452, 1996.
41. Gollob, J. A., Schnipper, C. P., Murphy, E. A., Ritz, J., and Frank, D. A. The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation. J. Immunol., 162: 4472-4481, 1999.
42. Mikovits, J. A., Young, H. A., Vertino, P., Issa, J. P., Pitha, P. M., Turcoski-Corrales, S., Taub, D. D., Petrow, C. L., Baylin, S. B., and Ruscetti, F. W. Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the γ interferon (IFN-γ) promoter and subsequent downregulation of IFN-γ production. Mol. Cell. Biol., 18: 5166-5177, 1998.
43. Cai, G., Kastelein, R. A., and Hunter, C. A. IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-γ when combined with IL-18. Eur. J. Immunol., 29: 2658-2665, 1999.
44. Rakhit, A., Yeon, M. M., Ferrante, J., Fettner, S., Nadeau, R., Motzer, R., Bukowski, R., Carvajal, D. M., Wilkinson, V. L., Presky, D. H., Magram, J., and Gately, M. K. Down-regulation of the pharmacokinetic-pharmacodynamic response to interleukin-12 during long-term administration to patients with renal cell carcinoma and evaluation of the mechanism of this "adaptive response" in mice. Clin. Pharmacol. Ther., 65: 615-629, 1999.
45. Stitt, J. T., DuBois, A. B., Douglas, J. S., and Shimada, S. G. Exhalation of gaseous nitric oxide by rats in response to endotoxin and its absorption by the lungs. J. Appl. Physiol., 82: 305-316, 1997.
46. Fujii, Y., Goldberg, P., and Hussain, S. N. Intrathoracic and extrathoracic sources of exhaled nitric oxide in porcine endotoxemic shock. Chest, 114: 569-576, 1998.