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MVA-MUC1-IL2 vaccine immunotherapy (TG4010) improves PSA doubling time in patients with prostate cancer with biochemical failure

  • PHASE II STUDIES
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Summary

Purpose: TG4010 is a recombinant MVA vector expressing the tumor-associated antigen MUC1 and IL2. We explored the effect two schedules of TG4010 on PSA in men with PSA progression. Patients and methods: A randomized phase II trial was conducted in 40 patients with PSA progression. Patients had PSA doubling times less than 10 months, with no overt evidence of disease. Patients received either weekly subcutaneous injection (sc) of TG4010 108 pfu for 6 weeks, then one injection every 3 weeks or sc injection of TG4010 108 pfu every 3 weeks. Results: The primary endpoint of a 50% decrease in PSA values from baseline was not observed. Nevertheless, 13 of 40 patients had a more than two fold improvement in PSA doubling time. Ten patients had their PSA stabilized for over 8 months. Therapy was well tolerated. Conclusions: Although the primary endpoint was not achieved, there is evidence of biologic activity of TG4010 in patients with PSA progression, further investigation in prostate cancer is warranted.

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References

  1. Kupelian P, Buchsbaum J, Patel C et al (2002) Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era. Int J Radiat Oncol Biol Phys 52:704–711 doi:10.1016/S0360-3016(01)02778-X

    Article  PubMed  CAS  Google Scholar 

  2. Amling C, Blute M, Bergstralh E, Seay T, Slezak J, Zincke H (2000) Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol 164:101–105 doi:10.1016/S0022-5347(05)67457-5

    Article  PubMed  CAS  Google Scholar 

  3. Pound C, Partin A, Epstein J, Walsh P (1997) Prostate-specific antigen after anatomic radical retropubic prostatectomy: patterns of recurrence and cancer control. Urol Clin North Am 24:395–406 doi:10.1016/S0094-0143(05)70386-4

    Article  PubMed  CAS  Google Scholar 

  4. Keating N, O’Malley A, Smith M (2006) Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24:4448–4456 doi:10.1200/JCO.2006.06.2497

    Article  PubMed  CAS  Google Scholar 

  5. Loblaw DA, Virgo KS, Nam R et al (2007) Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology Practice Guideline. J Clin Oncol 25(12):1596–1605 doi:10.1200/JCO.2006.10.1949

    Article  PubMed  CAS  Google Scholar 

  6. Taylor-Papadimitriou J, Burchell J, Plunkett T et al (2002) MUC1 and the immunobiology of cancer. J Mammary Gland Biol Neoplasia 7:209–221 doi:10.1023/A:1020360121451

    Article  PubMed  Google Scholar 

  7. Girling A, Bartkova J, Burchell J, Gendler S, Gillett C, Taylor-Papadimitriou J (1989) A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal antibody SM-3 is selectively exposed in a range of primary carcinomas. Int J Cancer 43:1072–1076 doi:10.1002/ijc.2910430620

    Article  PubMed  CAS  Google Scholar 

  8. Kirschenbaum A, Itzkowitz S, Wang J, Yao S, Eliashvili M, Levine A (1999) MUC1 expression in prostate carcinoma: correlation with grade and stage. Mol Urol 3:163–168

    PubMed  Google Scholar 

  9. Lapointe J, Li C, Higgins J et al (2004) Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 101:811–816 doi:10.1073/pnas.0304146101

    Article  PubMed  CAS  Google Scholar 

  10. Arai T, Fujita K, Fujime M, Irimura T (2005) Expression of sialylated MUC1 in prostate cancer: relationship to clinical stage and prognosis. Int J Urol 12:654–661 doi:10.1111/j.1442-2042.2005.01112.x

    Article  PubMed  CAS  Google Scholar 

  11. Goydos J, Elder E, Whiteside T, Finn O, Lotze M (1996) A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. J Surg Res 63:298–304 doi:10.1006/jsre.1996.0264

    Article  PubMed  CAS  Google Scholar 

  12. Brossart P, Wirths S, Stuhler G, Reichardt V, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96:3102–3108

    PubMed  CAS  Google Scholar 

  13. MacLean G, Reddish M, Koganty R, Longenecker B (1996) Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother Emphasis Tumor Immunol 19:59–68

    PubMed  CAS  Google Scholar 

  14. Scholl S, Squiban P, Bizouarne N et al (2003) Metastatic breast tumour regression following treatment by a gene-modified vaccinia virus expressing MUC1 and IL-2. J Biomed Biotechnol 2003(3):194–201 doi:10.1155/S111072430320704X

    Article  PubMed  Google Scholar 

  15. Pantuck A, van Ophoven A, Gitlitz B et al (2004) Phase I trial of antigen-specific gene therapy using a recombinant vaccinia virus encoding MUC-1 and IL-2 in MUC-1-positive patients with advanced prostate cancer. J Immunother 27:240–253 doi:10.1097/00002371-200405000-00009

    Article  PubMed  CAS  Google Scholar 

  16. Rochlitz C, Figlin R, Squiban P et al (2003) Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer. J Gene Med 5:690–699 doi:10.1002/jgm.397

    Article  PubMed  CAS  Google Scholar 

  17. Asai T, Storkus W, Whiteside T (2000) Evaluation of the modified ELISPOT assay for interferon-γ production in monitoring of cancer patients receiving antitumor vaccines. Clin Diagn Lab Immunol 7:145–154 doi:10.1128/CDLI.7.2.145-154.2000

    PubMed  CAS  Google Scholar 

  18. Schultes B, Whiteside T (2003) Monitoring of immune responses to CA125 with an IFN-γ ELISPOT assay. J Immunol Methods 279:1–15 doi:10.1016/S0022-1759(03)00253-9

    Article  PubMed  CAS  Google Scholar 

  19. Heukamp L, van der Burg S, Drijfhout J, Melief C, Taylor-Papadimitriou J, Offringa R (2001) Identification of three non-VNTR MUC1-derived HLA-A*0201-restricted T-cell epitopes that induce protective anti-tumor immunity in HLA-A2/K(b)-transgenic mice. Int J Cancer 91:385–392 doi:10.1002/1097-0215(200002)9999:9999<::AID-IJC1051>3.0.CO;2-Z

    Article  PubMed  CAS  Google Scholar 

  20. Brossart P, Spahlinger B, Grunebach F et al (1999) Induction of minor histocompatiblity antigen HA-1-specific cytotoxic T cells for the treatment of leukemia after allogeneic stem cell transplantation. Blood 94:4374–4376

    PubMed  CAS  Google Scholar 

  21. Shahinian V, Kuo Y, Freeman J, Orihuela E, Goodwin J (2005) Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer 103:1615–1624 doi:10.1002/cncr.20955

    Article  PubMed  CAS  Google Scholar 

  22. Tsai HK, D’Amico AV, Sadetsky N, Chen M-H, Carroll PR (2007) Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst 99(20):1516–1524 doi:10.1093/jnci/djm168

    Article  PubMed  Google Scholar 

  23. 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 doi:10.1200/JCO.2005.04.5252

    Article  PubMed  CAS  Google Scholar 

  24. Small EJ, Sacks N, Nemunaitis J et al (2007) Granulocyte macrophage colony-stimulating factor-secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin Cancer Res 13(13):3883–3891 doi:10.1158/1078-0432.CCR-06-2937

    Article  PubMed  CAS  Google Scholar 

  25. Rini B, Fong L, Weinberg V, Kavanaugh B, Small E (2006) Clinical and immunological characteristics of patients with serologic progression of prostate cancer achieving long-term disease control with granulocyte-macrophage colony-stimulating factor. J Urol 175:2087–2091 doi:10.1016/S0022-5347(06)00261-8

    Article  PubMed  Google Scholar 

  26. Dreicer R, Klein E, See W, Phase II (2001) Trial of GM-CSF in patients with advanced prostate cancer. Invest New Drugs 19:261–264 doi:10.1023/A:1010637105066

    Article  PubMed  CAS  Google Scholar 

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Dreicer, R., Stadler, W.M., Ahmann, F.R. et al. MVA-MUC1-IL2 vaccine immunotherapy (TG4010) improves PSA doubling time in patients with prostate cancer with biochemical failure. Invest New Drugs 27, 379–386 (2009). https://doi.org/10.1007/s10637-008-9187-3

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  • DOI: https://doi.org/10.1007/s10637-008-9187-3

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