Phase I/II randomized trial of dendritic cell vaccination with or without cyclophosphamide for consolidation therapy of advanced ovarian cancer in first or second remission

Cancer Immunology, Immunotherapy

Volumn 61, Issue 5, 2012, Pages 629-641

  Chu, Christina S ^a,b   Boyer, Jean ^a   Schullery, Daniel S ^a   Gimotty, Phyllis A ^c   Gamerman, Victoria ^c   Bender, James ^d,e   Levine, Bruce L ^a   Coukos, George ^a   Rubin, Stephen C ^a   Morgan, Mark A ^f   Vonderheide, Robert H ^g   June, Carl H ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b 3 West Pavilion Jordan Center for Gynecologic Cancer   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d Immuno Designed Molecules Inc   (United States)

^e ImmunoCellular Therapeutics   (United States)

^f FOX CHASE CANCER CENTER   (United States)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Clinical trial; Consolidation therapy; Dendritic cell; Ovarian cancer; Vaccine

Indexed keywords

CARBOPLATIN; CISPLATIN; CYCLOPHOSPHAMIDE; DENDRITIC CELL VACCINE; DIPHTHERIA TOXOID CRM197; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; PACLITAXEL; TELOMERASE REVERSE TRANSCRIPTASE;

ADVANCED CANCER; ARTICLE; BLOOD SAMPLING; CANCER GRADING; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER REGRESSION; CANCER SURVIVAL; CELLULAR IMMUNITY; CLINICAL ARTICLE; CONTROLLED STUDY; DENDRITIC CELL; DRUG EFFICACY; ENZYME LINKED IMMUNOSPOT ASSAY; FLOW CYTOMETRY; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE COUNT; OVARY CANCER; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REGULATORY T LYMPHOCYTE; SINGLE DRUG DOSE; SURVIVAL TIME;

ADOLESCENT; ADULT; BACTERIAL PROTEINS; CANCER VACCINES; COMBINED MODALITY THERAPY; CYCLOPHOSPHAMIDE; DENDRITIC CELLS; DRUG SYNERGISM; FEMALE; HUMANS; IMMUNOTHERAPY, ADOPTIVE; INTERFERON-GAMMA; MALARIA VACCINES; MIDDLE AGED; MONOCYTES; NEOPLASM RECURRENCE, LOCAL; NEUTROPHILS; OVARIAN NEOPLASMS; PEPTIDE FRAGMENTS; PNEUMOCOCCAL VACCINES; RECEPTOR, ERBB-2; SURVIVAL RATE; T-LYMPHOCYTES, REGULATORY; YOUNG ADULT;

EID: 84862495613     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-011-1081-8     Document Type: Article

References (46)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71-96 (Pubitemid 351521864)
2. Ozols RF (2002) Recurrent ovarian cancer: evidence-based treatment. J Clin Oncol 20:1161-1163
3. McGuire WP, Ozols RF (1998) Chemotherapy of advanced ovarian cancer. Semin Oncol 25:340-348 (Pubitemid 28272608)
4. Rubin SC, Randall TC, Armstrong KA, Chi DS, Hoskins WJ (1999) Ten-year follow-up of ovarian cancer patients after second-look laparotomy with negative findings. Obstet Gynecol 93:21-24
5. Zhang L, Conejo-Garcia JR, Katsaros D et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348:203-213 (Pubitemid 36077915)
6. Sabbatini P, Odunsi K (2007) Immunologic approaches to ovarian cancer treatment. J Clin Oncol 25:2884-2893 (Pubitemid 47123152)
7. Nelson BH (2008) The impact of T-cell immunity on ovarian cancer outcomes. Immunol Rev 222:101-116
8. Woo EY, Chu CS, Goletz TJ, Schlienger K, Coukos G, Rubin SC, Kaiser LR, June CH (2001) Regulatory CD4+CD25+ T cells in tumors from patients with early-stage non small cell lung cancer and late-stage ovarian cancer. Cancer Res 61:4766-4772 (Pubitemid 32691889)
9. Tange S, Scherer MN, Graeb C, Weiss T, Justl M, Frank E, Andrassy J, Jauch KW, Geissler EK (2002) The antineoplastic drug paclitaxel has immunosuppressive properties that can effectively promote allograft survival in a rat heart transplant model1. Transplantation 73:216
10. Si MS, Imagawa DK, Ji P, Wei X, Holm B, Kwok J, Lee M, Reitz BA, Borie DC (2003) Immunomodulatory effects of docetaxel on human lymphocytes. Investig New Drugs 21:281-290 (Pubitemid 37486330)
11. Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296-306 (Pubitemid 40516155)
12. Tacken PJ, de Vries IJ, Torensma R, Figdor CG (2007) Dendriticcell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 7:790-802 (Pubitemid 47480309)
13. Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, Davis MM, Engleman EG (2001) Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 98:8809-8814 (Pubitemid 32678109)
14. Kantoff PW, Higano CS, Shore ND et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411-422
15. Hellstrom I, Goodman G, Pullman J, Yang Y, Hellstrom KE (2001) Overexpression of HER-2 in ovarian carcinomas. Cancer Res 61:2420-2423 (Pubitemid 32685817)
16. Ross JS, Fletcher JA (1999) The HER-2/neu oncogene: prognostic factor, predictive factor and target for therapy. Semin Cancer Biol 9:125-138 (Pubitemid 29265528)
17. Vonderheide RH, Hahn WC, Schultze JL, Nadler LM (1999) The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 10:673-679 (Pubitemid 29302920)
18. Vonderheide RH (2002) Telomerase as a universal tumor-associated antigen for cancer immunotherapy. Oncogene 21:674-679
19. Alexander J, Sidney J, Southwood S et al (1994) Development of high potency universal DR-restricted helper epitopes by modification of high affinity DR-blocking peptides. Immunity 1:751-761
20. Wierecky J, Muller MR, Wirths S et al (2006) Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res 66:5910-5918 (Pubitemid 43927146)
21. Hung CF, Tsai YC, He L, Wu TC (2007) DNA vaccines encoding Ii-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency. Mol Ther 15:1211-1219 (Pubitemid 46813626)
22. Alexander J, del Guercio M, Maewal A et al (2000) Linear PADRE T helper epitope and carbohydrate B cell epitope conjugates induce specific high titer IgG antibody responses. J Immunol 164:1625
23. North RJ (1982) Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med 155:1063-1074
24. Berd D, Mastrangelo MJ, Engstrom PF, Paul A, Maguire H (1982) Augmentation of the human immune response by cyclophosphamide. Cancer Res 42:4862-4866 (Pubitemid 13206007)
25. Ercolini AM, Ladle BH, Manning EA et al (2005) Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J Exp Med 201:1591-1602 (Pubitemid 40723662)
26. Shah CA, Allison KH, Garcia RL, Gray HJ, Goff BA, Swisher EM (2008) Intratumoral T cells, tumor-associated macrophages, and regulatory T cells: association with p53 mutations, circulating tumor DNA and survival in women with ovarian cancer. Gynecol Oncol 109:215-219
27. Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942-949 (Pubitemid 39273735)
28. Sato E, Olson SH, Ahn J et al (2005) Intraepithelial CD8? tumorinfiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102:18538-18543 (Pubitemid 43011261)
29. Scardino A, Gross DA, Alves P et al (2002) HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy. J Immunol 168:5900-5906 (Pubitemid 34556179)
30. Zaks TZ, Rosenberg SA (1998) Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cytotoxic T lymphocytes that fail to recognize HER-2/neu? tumors. Cancer Res 58:4902-4908 (Pubitemid 28503688)
31. Knutson KL, Schiffman K, Cheever MA, Disis ML (2002) Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res 8:1014-1018 (Pubitemid 34517634)
32. Kono K, Takahashi A, Sugai H, Fujii H, Choudhury AR, Kiessling R, Matsumoto Y (2002) Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer. Clin Cancer Res 8:3394-3400 (Pubitemid 35340713)
33. Rongcun Y, Salazar-Onfray F, Charo J et al (1999) Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas. J Immunol 163:1037-1044 (Pubitemid 29328117)
34. Kavanagh B, Ko A, Venook A et al (2007) Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides. J Immunother 30:762-772 (Pubitemid 47480759)
35. Kamboj K, Kirchner H, Kimmel R, Greenspan N, Schreiber J (2003) Significant variation in serotype-specific immunogenicity of the seven-valent Streptococcus pneumoniae capsular polysaccharide-CRM-197 conjugate vaccine occurs despite vigorous T cell help induced by the carrier protein. J Infect Dis 187:1629-1638 (Pubitemid 36578969)
36. Rapoport A, Stadtmauer EA, Aqui N et al (2005) Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med 11:1230-1237 (Pubitemid 43093671)
37. Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR (2003) Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the gynecologic oncology group. J Clin Oncol 21:283-290 (Pubitemid 46606157)
38. Awwad M, North RJ (1989) Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells. Cancer Res 49:1649-1654 (Pubitemid 19108381)
39. Ghiringhelli F, Menard C, Puig P et al (2007) Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56:641-648 (Pubitemid 46348738)
40. Audia S, Nicolas A, Cathelin D et al (2007) Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25+ T lymphocytes. Clin Exp Immunol 150:523-530 (Pubitemid 350098743)
41. Laheru D, Lutz E, Burke J et al (2008) Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 14:1455-1463 (Pubitemid 351413929)
42. Emens L, Asquith J, Leatherman J et al (2009) Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J Clin Oncol 27:5911-5918
43. Colombo M, Piconese S (2007) Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer 7:880-887 (Pubitemid 350006256)
44. Greten T, Ormandy L, Fikuart A, Höchst B, Henschen S, Hörning M, Manns M, Korangy F (2010) Low-dose cyclophosphamide treatment impairs regulatory T cells and unmasks AFP-specific CD4+ T-cell responses in patients with advanced HCC. J Immunother 33:211-218
45. Buzzi S, Rubboli D, Buzzi G, Buzzi A, Morisi C, Pironi F (2004) CRM197 (nontoxic diphtheria toxin): effects on advanced cancer patients. Cancer Immunol Immunother 53:1041-1048 (Pubitemid 39371748)
46. Rapoport AP, Aqui NA, Stadtmauer EA et al (2011) Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination based on hTERT and survivin following ASCT for myeloma. Blood 117:788-797