An integrated disease/pharmacokinetic/pharmacodynamic model suggests improved interleukin-21 regimens validated prospectively for mouse solid cancers

PLoS Computational Biology

Volumn 7, Issue 9, 2011, Pages

  Elishmereni, Moran ^a   Kheifetz, Yuri ^a   Søndergaard, Henrik ^b   Overgaard, Rune Viig ^b   Agur, Zvia ^a,c  

^a Institute for Medical Biomathematics Isarel   (Israel)

^b NOVO NORDISK A S   (Denmark)

^c Optimata Ltd   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

DERMATOLOGY; MAMMALS; ONCOLOGY; TUMORS;

'CURRENT; ANTITUMOUR AGENTS; CANCER PATIENTS; CONDITION; CYTOKINES; IMMUNOMODULATORY; INTERLEUKIN-21; PARTIAL RESPONSE; PHARMACOKINETIC PHARMACODYNAMIC MODELS; SOLID CANCER;

DISEASES;

INTERLEUKIN 21; ANTINEOPLASTIC AGENT; INTERLEUKIN DERIVATIVE;

ACCURACY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER IMMUNOTHERAPY; COMPUTER MODEL; CONTROLLED STUDY; DISEASE MODEL; DRUG ABSORPTION; DRUG EFFICACY; DRUG EXCRETION; DRUG RESPONSE; DRUG TRANSPORT; IN VIVO STUDY; KIDNEY CARCINOMA; LOW DRUG DOSE; MATHEMATICAL MODEL; MELANOMA; MOUSE; NONHUMAN; PHARMACODYNAMICS; PREDICTION; PROSPECTIVE STUDY; RETROSPECTIVE STUDY; SIMULATION; SINGLE DRUG DOSE; SOLID TUMOR; ANIMAL; BIOLOGICAL MODEL; COMPUTER SIMULATION; DOSE RESPONSE; DRUG ADMINISTRATION; EXPERIMENTAL NEOPLASM; METABOLISM; REPRODUCIBILITY;

MURINAE; MUS;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COMPUTER SIMULATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; INTERLEUKINS; MICE; MODELS, BIOLOGICAL; NEOPLASMS, EXPERIMENTAL; REPRODUCIBILITY OF RESULTS;

EID: 80053435113     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1002206     Document Type: Article

References (54)

1. Finn OJ, (2008) Cancer immunology. N Engl J Med 358: 2704-2715.
2. Kirkwood JM, Tarhini AA, Panelli MC, Moschos SJ, Zarour HM, et al. (2008) Next generation of immunotherapy for melanoma. J Clin Oncol 26: 3445-3455.
3. Ribas A, (2006) Update on immunotherapy for melanoma. J Natl Compr Canc Netw 4: 687-694.
4. Davis ID, Skak K, Smyth MJ, Kristjansen PE, Miller DM, et al. (2007) Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res 13: 6926-6932.
5. di Carlo E, de Totero D, Piazza T, Fabbi M, Ferrini S, (2007) Role of IL-21 in immune-regulation and tumor immunotherapy. Cancer Immunol Immunother 56: 1323-1334.
6. Leonard WJ, Spolski R, (2005) Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol 5: 688-698.
7. Leonard WJ, Zeng R, Spolski R, (2008) Interleukin 21: a cytokine/cytokine receptor system that has come of age. J Leukoc Biol 84: 348-356.
8. Sondergaard H, Skak K, (2009) IL-21: roles in immunopathology and cancer therapy. Tissue Antigens 74: 467-479.
9. Skak K, Kragh M, Hausman D, Smyth MJ, Sivakumar PV, (2008) Interleukin 21: combination strategies for cancer therapy. Nat Rev Drug Discov 7: 231-240.
10. Curti BD, (2006) Immunomodulatory and antitumor effects of interleukin-21 in patients with renal cell carcinoma. Expert Rev Anticancer Ther 6: 905-909.
11. Davis ID, Brady B, Kefford RF, Millward M, Cebon J, et al. (2009) Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial. Clin Cancer Res 15: 2123-2129.
12. Davis ID, Skrumsager BK, Cebon J, Nicholaou T, Barlow JW, et al. (2007) An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin Cancer Res 13: 3630-3636.
13. Thompson JA, Curti BD, Redman BG, Bhatia S, Weber JS, et al. (2008) Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma. J Clin Oncol 26: 2034-2039.
14. Schmidt H, Brown J, Mouritzen U, Selby P, Fode K, et al. (2010) Safety and clinical effect of subcutaneous human interleukin-21 in patients with metastatic melanoma or renal cell carcinoma: a phase I trial. Clin Cancer Res 16: 5312-5319.
15. Hashmi MH, Van Veldhuizen PJ, (2010) Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma. Expert Opin Biol Ther 10: 807-817.
16. Ansen S, Butler MO, Berezovskaya A, Murray AP, Stevenson K, et al. (2008) Dissociation of its opposing immunologic effects is critical for the optimization of antitumor CD8+ T-cell responses induced by interleukin 21. Clin Cancer Res 14: 6125-6136.
17. Kim-Schulze S, Kim HS, Fan Q, Kim DW, Kaufman HL, (2009) Local IL-21 promotes the therapeutic activity of effector T cells by decreasing regulatory T cells within the tumor microenvironment. Mol Ther 17: 380-388.
18. Castermans K, Tabruyn SP, Zeng R, van Beijnum JR, Eppolito C, et al. (2008) Angiostatic activity of the anti-tumor cytokine interleukin-21. Blood 112: 4940-4947.
19. Agur Z, Arakelyan L, Daugulis P, Ginosar Y, (2004) Hopf point analysis for angiogenesis models. Discrete and Continuous Dynamics- Series B 4: 29-38.
20. Arakelyan L, Vainstein V, Agur Z, (2002) A computer algorithm describing the process of vessel formation and maturation, and its use for predicting the effects of anti-angiogenic and anti-maturation therapy on vascular tumor growth. Angiogenesis 5: 203-214.
21. de Pillis LG, Radunskaya AE, (2001) A mathematical tumor model with immune resistance and drug therapy: an optimal control approach. J Theor Med 3: 79-100.
22. Hart D, Shochat E, Agur Z, (1998) The growth law of primary breast cancer as inferred from mammography screening trials data. Br J Cancer 78: 382-387.
23. Kirschner D, Panetta JC, (1998) Modeling immunotherapy of the tumor-immune interaction. J Math Biol 37: 235-252.
24. Forys U, Kheifetz Y, Kogan Y, (2005) Critical-point analysis for three-variable cancer angiogenesis models. Math Biosci Eng 2: 511-525.
25. Cojocaru L, Agur Z, (1992) A theoretical analysis of interval drug dosing for cell-cycle-phase-specific drugs. Math Biosci 109: 85-97.
26. Abbott LH, Michor F, (2006) Mathematical models of targeted cancer therapy. Br J Cancer 95: 1136-1141.
27. Acharya RS, Sundareshan MK, (1984) Development of optimal drug administration strategies for cancer-chemotherapy in the framework of systems theory. Int J Biomed Comput 15: 139-150.
28. Agur Z, (1986) The effect of drug schedule to responsiveness of chemotherapy. Annals NY Acad Sci 504: 274-277.
29. Agur Z, Arnon R, Schechter B, (1988) Reduction of cytotoxicity to normal tissues by new regimens of phase-specific drugs. Mathematical Biosciences 92: 1-15.
30. Agur Z, Arnon R, Schechter B, (1992) Effect of the dosing interval on myelotoxicity and survival in mice treated by cytarabine. Eur J Cancer 28A: 1085-1090.
31. de Pillis LG, Gu W, Radunskaya AE, (2006) Mixed immunotherapy and chemotherapy of tumors: modeling, applications and biological interpretations. J Theor Biol 238: 841-862.
32. Gorelik B, Ziv I, Shohat R, Wick M, Hankins WD, et al. (2008) Efficacy of weekly docetaxel and bevacizumab in mesenchymal chondrosarcoma: a new theranostic method combining xenografted biopsies with a mathematical model. Cancer Res 68: 9033-9040.
33. Nani F, Freedman HI, (2000) A mathematical model of cancer treatment by immunotherapy. Math Biosci 163: 159-199.
34. Skomorovski K, Harpak H, Ianovski A, Vardi M, Visser TP, et al. (2003) New TPO treatment schedules of increased safety and efficacy: pre-clinical validation of a thrombopoiesis simulation model. Br J Haematol 123: 683-691.
35. Vainstein V, Ginosar Y, Shoham M, Ianovski A, Rabinovich A, et al. (2006) Improving cancer therapy by doxorubicin and granulocyte colony-stimulating factor: insights from a computerized model of human granulopoiesis. Mathematical Modelling of Natural Phenomena 1: 70-80.
36. Panetta JC, Schaiquevich P, Santana VM, Stewart CF, (2008) Using pharmacokinetic and pharmacodynamic modeling and simulation to evaluate importance of schedule in topotecan therapy for pediatric neuroblastoma. Clin Cancer Res 14: 318-325.
37. Gieschke R, Steimer JL, (2000) Pharmacometrics: modelling and simulation tools to improve decision making in clinical drug development. Eur J Drug Metab Pharmacokinet 25: 49-58.
38. van Kesteren C, Mathot RA, Beijnen JH, Schellens JH, (2003) Pharmacokinetic-pharmacodynamic guided trial design in oncology. Invest New Drugs 21: 225-241.
39. Cappuccio A, Elishmereni M, Agur Z, (2006) Cancer immunotherapy by interleukin-21: potential treatment strategies evaluated in a mathematical model. Cancer Res 66: 7293-7300.
40. Cappuccio A, Elishmereni M, Agur Z, (2007) Optimization of interleukin-21 immunotherapeutic strategies. J Theor Biol 248: 259-266.
41. Sondergaard H, Frederiksen KS, Thygesen P, Galsgaard ED, Skak K, et al. (2007) Interleukin 21 therapy increases the density of tumor infiltrating CD8(+)T cells and inhibits the growth of syngeneic tumors. Cancer Immunol Immunother. 56: 1417-1428.
42. Anderson DR, Burhnham KP, Thompson WL, (2000) Null hypothesis testing: problems, prevalence, and an alternative. Journal of wildlife management 64: 912-923.
43. Burhnham KP, Anderson DR, (2001) Kullback-Leibler information as a basis for strong inference in ecological studies. Wildlife research 28: 111-119.
44. Karlsson MO, Molnar V, Freijs A, Nygren P, Bergh J, et al. (1999) Pharmacokinetic models for the saturable distribution of paclitaxel. Drug Metab Dispos 27: 1220-1223.
45. Piscitelli SC, Reiss WG, Figg WD, Petros WP, (1997) Pharmacokinetic studies with recombinant cytokines. Scientific issues and practical considerations. Clin Pharmacokinet 32: 368-381.
46. Overgaard RV, Holford N, Rytved KA, Madsen H, (2007) PKPD Model of Interleukin-21 Effects on Thermoregulation in Monkeys-Application and Evaluation of Stochastic Differential Equations. Pharm Res 24: 298-309.
47. Overgaard RV, Karlsson M, Ingwersen SH, (2007) Pharmacodynamic model of interleukin-21 effects on red blood cells in cynomolgus monkeys. J Pharmacokinet Pharmacodyn 34: 559-574.
48. Hooke R, Jeeves TA, (1961) Direct Search Solution of Numerical and Statistical Problems. J ACM 8: 212-229.
49. Agur Z, Hassin R, Levi S, (2006) Optimizing chemotherapy scheduling using local search heuristics. Operations Research 54: 829-846.
50. Cheever MA, (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222: 357-368.
51. Hinrichs CS, Spolski R, Paulos CM, Gattinoni L, Kerstann KW, et al. (2008) IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 111: 5326-5333.
52. Marzec M, Halasa K, Kasprzycka M, Wysocka M, Liu X, et al. (2008) Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells. Cancer Res 68: 1083-1091.
53. Sondergaard H, Galsgaard ED, Bartholomaeussen M, Straten PT, Odum N, et al. (2010) Intratumoral interleukin-21 increases antitumor immunity, tumor-infiltrating CD8+ T-cell density and activity, and enlarges draining lymph nodes. J Immunother 33: 236-249.
54. Rosenthal DI, Ang KK, (2004) Altered radiation therapy fractionation, chemoradiation, and patient selection for the treatment of head and neck squamous carcinoma. Semin Radiat Oncol 14: 153-166.