Skip to main content
SpringerLink
Log in

Issues in Pre-clinical Models, Clinical Trial Design and Analytical Considerations in Developing and Evaluating Novel Cancer Immunotherapies

  • Chapter
  • First Online:
Cancer Immunotherapy

  • 2446 Accesses

Abstract

The role of the immune system in detecting and killing cancer cells has been understood for decades1–3. The human immune system has an innate ability to arrest carcinogenesis; however, in some cases, this system fails due to a series of mechanisms that tumor cells use to escape immune surveillance, such as mimicking normal cells, producing immunosuppressive growth factors and cytokines, or forming complex immunological interactions4. Differences in clinical responses to immunotherapy differ sufficiently from responses to cytotoxic agents that many aspects of clinical trial design must be re-thought, the subject of this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Oliver RT, Nouri AM (1992) T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy. Cancer Surv 13:173–204

    PubMed  CAS  Google Scholar 

  2. Hellstrom IE, Hellstrom KE, Pierce GE, Bill AH (1968) Demonstration of cell-bound and humoral immunity against neuroblastoma cells. Proc Natl Acad Sci USA 60(4):1231–1238

    Article  PubMed  CAS  Google Scholar 

  3. Vose BM, Moore M (1985) Human tumor-infiltrating lymphocytes: a marker of host response. Semin Hematol 22(1):27–40

    PubMed  CAS  Google Scholar 

  4. Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S (2000) Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 74:181–273

    Article  PubMed  CAS  Google Scholar 

  5. Tanaka K, Tanahashi N, Tsurumi C, Yokota KY, Shimbara N (1997) Proteasomes and antigen processing. Adv Immunol 64:1–38

    Article  PubMed  CAS  Google Scholar 

  6. Hammer GE, Kanaseki T, Shastri N (2007) The final touches make perfect the peptide-MHC class I repertoire. Immunity 26(4):397–406

    Article  PubMed  CAS  Google Scholar 

  7. Chomarat P, Banchereau J (1998) Interleukin-4 and interleukin-13: their similarities and discrepancies. Int Rev Immunol 17(1–4):1–52

    Article  PubMed  CAS  Google Scholar 

  8. Parmiani G, Russo V, Marrari A et al (2007) Universal and stemness-related tumor antigens: potential use in cancer immunotherapy. Clin Cancer Res 13(19):5675–5679

    Article  PubMed  CAS  Google Scholar 

  9. Small EJ, Schellhammer PF, Higano CS et al (2006) Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 24(19):3089–3094

    Article  PubMed  CAS  Google Scholar 

  10. Kantoff PW, Schuetz TJ, Blumenstein BA et al (2010) Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 28(7):1099–1105

    Article  PubMed  CAS  Google Scholar 

  11. Schellhammer P, Higano C, Berger E, et al. A randomized, double-blind, placebo-controlled, multi-center, phase III trial of sipuleucel-T in men with metastatic, androgen independent prostatic adenocarcinoma (AIPC) [abstract]. Available from: http://www.aua2009.org/program/lbsciforum.asp

  12. Schlom J, Arlen PM, Gulley JL (2007) Cancer vaccines: moving beyond current paradigms. Clin Cancer Res 13(13):3776–3782

    Article  PubMed  CAS  Google Scholar 

  13. Eaton JD, Perry MJ, Nicholson S et al (2002) Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer. BJU Int 89(1):19–26

    Article  PubMed  CAS  Google Scholar 

  14. Ward JE, McNeel DG (2007) GVAX: an allogeneic, whole-cell, GM-CSF-secreting cellular immunotherapy for the treatment of prostate cancer. Expert Opin Biol Ther 7(12):1893–1902

    Article  PubMed  CAS  Google Scholar 

  15. Madan RA, Gulley JL, Schlom J et al (2008) Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy. Clin Cancer Res 14(14):4526–4531

    Article  PubMed  CAS  Google Scholar 

  16. Hsu FJ, Caspar CB, Czerwinski D et al (1997) Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma–long-term results of a clinical trial. Blood 89(9):3129–3135

    PubMed  CAS  Google Scholar 

  17. Riethmuller G, Holz E, Schlimok G et al (1998) Monoclonal antibody therapy for resected Dukes’ C colorectal cancer: seven-year outcome of a multicenter randomized trial. J Clin Oncol 16(5):1788–1794

    PubMed  CAS  Google Scholar 

  18. Morton DL, Ollila DW, Hsueh EC, Essner R, Gupta RK (1999) Cytoreductive surgery and adjuvant immunotherapy: a new management paradigm for metastatic melanoma. CA Cancer J Clin 49(2):101–116, 65

    Article  PubMed  CAS  Google Scholar 

  19. Fu T, Shen Y, Fujimoto S (2000) Tumor-specific CD4(+) suppressor T-cell clone capable of inhibiting rejection of syngeneic sarcoma in A/J mice. Int J Cancer 87(5):680–687

    Article  PubMed  CAS  Google Scholar 

  20. Ghiringhelli F, Larmonier N, Schmitt E et al (2004) CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34(2):336–344

    Article  PubMed  CAS  Google Scholar 

  21. Teicher BA (2007) Transforming growth factor-beta and the immune response to malignant disease. Clin Cancer Res 13(21):6247–6251

    Article  PubMed  CAS  Google Scholar 

  22. Muller AJ, Prendergast GC (2007) Indoleamine 2,3-dioxygenase in immune suppression and cancer. Curr Cancer Drug Targets 7(1):31–40

    Article  PubMed  CAS  Google Scholar 

  23. von Mehren M, Arlen P, Gulley J et al (2001) he influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma. Clin Cancer Res 7(5):1181–1191

    Google Scholar 

  24. Madan RA, Mohebtash M, Schlom J, Gulley JL (2010) Therapeutic vaccines in metastatic castration-resistant prostate cancer: principles in clinical trial design. Expert Opin Biol Ther 10(1):19–28

    Article  PubMed  Google Scholar 

  25. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    Article  PubMed  CAS  Google Scholar 

  26. Therasse P, Eisenhauer EA, Verweij J (2006) RECIST revisited: a review of validation studies on tumour assessment. Eur J Cancer 42(8):1031–1039

    Article  PubMed  CAS  Google Scholar 

  27. Gulley JL, Arlen PM, Tsang KY et al (2008) Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res 14(10):3060–3069

    Article  PubMed  CAS  Google Scholar 

  28. Jones RL, Cunningham D, Cook G, Ell PJ (2004) Tumour vaccine associated lymphadenopathy and false positive positron emission tomography scan changes. Br J Radiol 77(913):74–75

    Article  PubMed  CAS  Google Scholar 

  29. Loveland BE, Zhao A, White S et al (2006) Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma. Clin Cancer Res 12(3 Pt 1):869–877

    Article  PubMed  CAS  Google Scholar 

  30. Saenger YM, Wolchok JD (2008) The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: patient cases. Cancer Immun 8:1

    PubMed  Google Scholar 

  31. Weber J, Thompson JA, Hamid O et al (2009) A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res 15(17):5591–5598

    Article  PubMed  CAS  Google Scholar 

  32. Wolchok JD, Neyns B, Linette G et al (2010) Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 11(2):155–164

    Article  PubMed  CAS  Google Scholar 

  33. Wolchok JD, Hoos A, O’Day S et al (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15(23):7412–7420

    Article  PubMed  CAS  Google Scholar 

  34. Hoos A, Eggermont AM, Janetzki S et al (2010) Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 102(18):1388–1397

    Article  PubMed  CAS  Google Scholar 

  35. Finke LH, Wentworth K, Blumenstein B, Rudolph NS, Levitsky H, Hoos A (2007) Lessons from randomized phase III studies with active cancer immunotherapies–outcomes from the 2006 meeting of the Cancer Vaccine Consortium (CVC). Vaccine 25(suppl 2):B97–B109

    Article  PubMed  CAS  Google Scholar 

  36. Tang PA, Bentzen SM, Chen EX, Siu LL (2007) Surrogate end points for median overall survival in metastatic colorectal cancer: literature-based analysis from 39 randomized controlled trials of first-line chemotherapy. J Clin Oncol 25(29):4562–4568

    Article  PubMed  Google Scholar 

  37. Panageas KS, Ben-Porat L, Dickler MN, Chapman PB, Schrag D (2007) When you look matters: the effect of assessment schedule on progression-free survival. J Natl Cancer Inst 99(6):428–432

    Article  PubMed  Google Scholar 

  38. Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676

    Article  PubMed  CAS  Google Scholar 

  39. Wolmark N, Yothers G, O’Connell M et al (2009) A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: results of NSABP Protocol C-08 [abstract]. J Clin Oncol 27:18s, LBA4

    Article  Google Scholar 

  40. Kantoff PW, Higano CS, Shore ND et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422

    Article  PubMed  CAS  Google Scholar 

  41. Madan RA, Gulley JL, Fojo T, Dahut WL (2010) Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression. Oncologist 15(9):969–975

    Article  PubMed  Google Scholar 

  42. Burch PA, Breen JK, Buckner JC et al (2000) Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clin Cancer Res 6(6):2175–2182

    PubMed  CAS  Google Scholar 

  43. Burch PA, Croghan GA, Gastineau DA et al (2004) Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer: a Phase 2 trial. Prostate 60(3):197–204

    Article  PubMed  CAS  Google Scholar 

  44. Small EJ, Fratesi P, Reese DM et al (2000) Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 18(23):3894–3903

    PubMed  CAS  Google Scholar 

  45. Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  PubMed  CAS  Google Scholar 

  46. Gulley JL, Arlen PM, Bastian A et al (2005) Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res 11(9):3353–3362

    Article  PubMed  CAS  Google Scholar 

  47. Kudo-Saito C, Schlom J, Hodge JW (2005) Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses. Clin Cancer Res 11(6):2416–2426

    Article  PubMed  CAS  Google Scholar 

  48. Gulley JL, Madan RA, Arlen PM (2007) Enhancing efficacy of therapeutic vaccinations by combination with other modalities. Vaccine 25(suppl 2):B89–B96

    Article  PubMed  CAS  Google Scholar 

  49. Ma Y, Kepp O, Ghiringhelli F et al (2010) Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin Immunol 22(3):113–124

    Article  PubMed  Google Scholar 

  50. Zitvogel L, Apetoh L, Ghiringhelli F, Andre F, Tesniere A, Kroemer G (2008) The anticancer immune response: indispensable for therapeutic success? J Clin Invest 118(6):1991–2001

    Article  PubMed  CAS  Google Scholar 

  51. Cheever MA, Schlom J, Weiner LM et al (2008) Translational Research Working Group developmental pathway for immune response modifiers. Clin Cancer Res 14(18):5692–5699

    Article  PubMed  CAS  Google Scholar 

  52. Hoos A, Parmiani G, Hege K et al (2007) A clinical development paradigm for cancer vaccines and related biologics. J Immunother 30(1):1–15

    Article  PubMed  Google Scholar 

  53. de Bono JS, Ashworth A (2010) Translating cancer research into targeted therapeutics. Nature 467(7315):543–549

    Article  PubMed  Google Scholar 

  54. Keilholz U, Martus P, Scheibenbogen C (2006) Immune monitoring of T-cell responses in cancer vaccine development. Clin Cancer Res 12(7 Pt 2):2346s–2352s

    Article  PubMed  CAS  Google Scholar 

  55. Altman JD, Moss PA, Goulder PJ et al (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274(5284):94–96

    Article  PubMed  CAS  Google Scholar 

  56. Czerkinsky C, Andersson G, Ekre HP, Nilsson LA, Klareskog L, Ouchterlony O (1988) Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods 110(1):29–36

    Article  PubMed  CAS  Google Scholar 

  57. Ryan JE, Ovsyannikova IG, Dhiman N et al (2005) Inter-operator variation in ELISPOT analysis of measles virus-specific IFN-gamma-secreting T cells. Scand J Clin Lab Invest 65(8):681–689

    Article  PubMed  CAS  Google Scholar 

  58. Cox JH, Ferrari G, Kalams SA, Lopaczynski W, Oden N, D’Souza MP (2005) Results of an ELISPOT proficiency panel conducted in 11 laboratories participating in international human immunodeficiency virus type 1 vaccine trials. AIDS Res Hum Retroviruses 21(1):68–81

    Article  PubMed  CAS  Google Scholar 

  59. Britten CM, Meyer RG, Kreer T, Drexler I, Wolfel T, Herr W (2002) The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. J Immunol Methods 259(1–2):95–110

    Article  PubMed  CAS  Google Scholar 

  60. Graca L (2005) New tools to identify regulatory T cells. Eur J Immunol 35(6):1678–1680

    Article  PubMed  CAS  Google Scholar 

  61. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061

    Article  PubMed  CAS  Google Scholar 

  62. Wieczorek G, Asemissen A, Model F et al (2009) Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res 69(2):599–608

    Article  PubMed  CAS  Google Scholar 

  63. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174

    Article  PubMed  CAS  Google Scholar 

  64. Lechner MG, Liebertz DJ, Epstein AL (2010) Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 185(4):2273–2284

    Article  PubMed  CAS  Google Scholar 

  65. Hernandez-Fuentes MP, Warrens AN, Lechler RI (2003) Immunologic monitoring. Immunol Rev 196:247–264

    Article  PubMed  CAS  Google Scholar 

  66. Sheikh NA, Jones LA (2008) CD54 is a surrogate marker of antigen presenting cell activation. Cancer Immunol Immunother 57(9):1381–1390

    Article  PubMed  CAS  Google Scholar 

  67. Higano CS, Schellhammer PF, Small EJ et al (2009) Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 115(16):3670–3679

    Article  PubMed  CAS  Google Scholar 

  68. Simon R (2008) Lost in translation: problems and pitfalls in translating laboratory observations to clinical utility. Eur J Cancer 44(18):2707–2713

    Article  PubMed  Google Scholar 

  69. Ozoren N, El-Deiry WS (2003) Cell surface Death Receptor signaling in normal and cancer cells. Semin Cancer Biol 13(2):135–147

    Article  PubMed  Google Scholar 

  70. Quarmby S, Hunter RD, Kumar S (2000) Irradiation induced expression of CD31, ICAM-1 and VCAM-1 in human microvascular endothelial cells. Anticancer Res 20(5B):3375–3381

    PubMed  CAS  Google Scholar 

  71. Friedman EJ (2002) Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des 8(19):1765–1780

    Article  PubMed  CAS  Google Scholar 

  72. Chakraborty M, Abrams SI, Camphausen K et al (2003) Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J Immunol 170(12):6338–6347

    PubMed  CAS  Google Scholar 

  73. Aquino A, Prete SP, Greiner JW et al (1998) Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells. Clin Cancer Res 4(10):2473–2481

    PubMed  CAS  Google Scholar 

  74. AbdAlla EE, Blair GE, Jones RA, Sue-Ling HM, Johnston D (1995) Mechanism of synergy of levamisole and fluorouracil: induction of human leukocyte antigen class I in a colorectal cancer cell line. J Natl Cancer Inst 87(7):489–496

    Article  PubMed  CAS  Google Scholar 

  75. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G (2008) Immunological aspects of cancer chemotherapy. Nat Rev Immunol 8(1):59–73

    Article  PubMed  CAS  Google Scholar 

  76. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H (2005) Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105(7):2862–2868

    Article  PubMed  CAS  Google Scholar 

  77. Maccubbin DL, Wing KR, Mace KF, Ho RL, Ehrke MJ, Mihich E (1992) Adriamycin-induced modulation of host defenses in tumor-bearing mice. Cancer Res 52(13):3572–3576

    PubMed  CAS  Google Scholar 

  78. Chan OT, Yang LX (2000) The immunological effects of taxanes. Cancer Immunol Immunother 49(4–5):181–185

    Article  PubMed  CAS  Google Scholar 

  79. Mercader M, Bodner BK, Moser MT et al (2001) T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci USA 98(25):14565–14570

    Article  PubMed  CAS  Google Scholar 

  80. Aragon-Ching JB, Williams KM, Gulley JL (2007) Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer. Front Biosci 12:4957–4971

    Article  PubMed  CAS  Google Scholar 

  81. Drake CG, Doody AD, Mihalyo MA et al (2005) Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen. Cancer Cell 7(3):239–249

    Article  PubMed  CAS  Google Scholar 

  82. Sutherland JS, Goldberg GL, Hammett MV et al (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175(4):2741–2753

    PubMed  CAS  Google Scholar 

  83. Wang J, Zhang Q, Jin S et al (2009) Immoderate inhibition of estrogen by anastrozole enhances the severity of experimental polyarthritis. Exp Gerontol 44(6–7):398–405

    PubMed  CAS  Google Scholar 

  84. Lenahan C, Cho D, Bissonnette A et al (2008) Immunologic effects of sunitinib in renal cell carcinoma [abstract]. J Clin Oncol 26(15S):14551

    Google Scholar 

  85. Farsaci B, Sabzevari H, Higgins JP et al (2010) Effect of a small molecule BCL-2 inhibitor on immune function and use with a recombinant vaccine. Int J Cancer 127(7):1603–1613

    Article  PubMed  CAS  Google Scholar 

  86. Ferrara TA, Hodge JW, Gulley JL (2009) Combining radiation and immunotherapy for synergistic antitumor therapy. Curr Opin Mol Ther 11(1):37–42

    PubMed  CAS  Google Scholar 

  87. Chi KH, Liu SJ, Li CP et al (2005) Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother 28(2):129–135

    Article  PubMed  Google Scholar 

  88. Fisk B, Ioannides CG (1998) Increased sensitivity of adriamycin-selected tumor lines to CTL-mediated lysis results in enhanced drug sensitivity. Cancer Res 58(21):4790–4793

    PubMed  CAS  Google Scholar 

  89. Matsuzaki I, Suzuki H, Kitamura M, Minamiya Y, Kawai H, Ogawa J (2000) Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells. Oncology 59(4):336–343

    Article  PubMed  CAS  Google Scholar 

  90. Garnett CT, Schlom J, Hodge JW (2008) Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res 14(11):3536–3544

    Article  PubMed  CAS  Google Scholar 

  91. Arlen PM, Gulley JL, Parker C et al (2006) A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 12(4):1260–1269

    Article  PubMed  CAS  Google Scholar 

  92. Gribben JG, Ryan DP, Boyajian R et al (2005) Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res 11(12):4430–4436

    Article  PubMed  CAS  Google Scholar 

  93. Antonia SJ, Mirza N, Fricke I et al (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12(3 Pt 1):878–887

    Article  PubMed  CAS  Google Scholar 

  94. Halabi S, Small EJ, Kantoff PW et al (2003) Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol 21(7):1232–1237

    Article  PubMed  Google Scholar 

  95. Docetaxel and Prednisone With or Without Vaccine Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT01145508

  96. Bhogal N, Combes R (2006) TGN1412: time to change the paradigm for the testing of new pharmaceuticals. Altern Lab Anim 34(2):225–239

    PubMed  CAS  Google Scholar 

  97. Renders L, Valerius T (2003) Engineered CD3 antibodies for immunosuppression. Clin Exp Immunol 133(3):307–309

    Article  PubMed  CAS  Google Scholar 

  98. Sheridan C (2006) TeGenero fiasco prompts regulatory rethink. Nat Biotechnol 24(5):475–476

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Building 10 Rm. 8B09, 10 Center Drive, Bethesda, MD, 20892, USA

    Marijo Bilusic, Ravi A. Madan & James L. Gulley

Authors
  1. Marijo Bilusic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ravi A. Madan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James L. Gulley
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. San Antonio Cancer Center, Babcock Road 2040, San Antonio, 78229, Texas, USA

    Tyler J. Curiel

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bilusic, M., Madan, R.A., Gulley, J.L. (2013). Issues in Pre-clinical Models, Clinical Trial Design and Analytical Considerations in Developing and Evaluating Novel Cancer Immunotherapies. In: Curiel, T. (eds) Cancer Immunotherapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4732-0_15

Download citation

Publish with us

Policies and ethics

Search

Navigation