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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2007

Open Access 01-12-2007 | Research

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Authors: Howard L Kaufman, Seunghee Kim-Schulze, Kelledy Manson, Gail DeRaffele, Josephine Mitcham, Kang Seok Seo, Dae Won Kim, John Marshall

Published in: Journal of Translational Medicine | Issue 1/2007

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Abstract

Purpose

An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.

Patients and methods

Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis.

Results

The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002).

Conclusion

Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.
Appendix
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Literature
1.
2.
Li D, Xie K, Wolff R, Abbruzzese JL: Pancreatic cancer. Lancet. 2004, 363: 1049-1057. 10.1016/S0140-6736(04)15841-8.CrossRefPubMed
3.
Ko AH, Dito E, Schillinger B, Venook AP, Bergsland EK, Tempero MA: Phase II study of fixed dose rate gemcitabine with cisplatin for metastatic adenocarcinoma of the pancreas. J Clin Oncol. 2006, 24: 379-385. 10.1200/JCO.2005.01.8267.CrossRefPubMed
4.
Tempero M, Alasadi R, Behrman S: Clinical practice guidelines in oncology. Pancreatic Adenocarcinoma. National Comprehensive Cancer Network. 2006, [http://​www.​nccn.​org]
5.
Laheru D, Jaffee EM: Immunotherapy for pancreatic cancer – science driving clinical progress. Nat Rev Cancer. 2005, 5: 459-467. 10.1038/nrc1630.CrossRefPubMed
6.
Tsang KY, Palena C, Gulley J, Arlen P, Schlom J: A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1. Clin Cancer Res. 2004, 10: 2139-2149. 10.1158/1078-0432.CCR-1011-03.CrossRefPubMed
7.
Finn OJ, Jerome KR, Henderson RA, Pecher G, Domenech N, Magarian-Blander J, Barratt-Boyes SM: MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev. 1995, 145: 61-89. 10.1111/j.1600-065X.1995.tb00077.x.CrossRefPubMed
8.
Aarts WM, Schlom J, Hodge JW: Vector-based vaccine/cytokine combination therapy to enhance induction of immune responses to a self-antigen and antitumor activity. Cancer Res. 2002, 62: 5770-5777.PubMed
9.
Tsang KY, Palena C, Yokokawa J, Arlen PM, Gulley JL, Mazzara GP, Gritz L, Gomez Yafal A, Ogueta S, Greenhalgh P: Analyses of Recombinant Vaccinia and Fowlpox Vaccine Vectors Expressing Transgenes for Two Human Tumor Antigens and Three Human Costimulatory Molecules. Clin Cancer Res. 2005, 11: 1597-1607. 10.1158/1078-0432.CCR-04-1609.CrossRefPubMed
10.
Pantuck AJ, van Ophoven A, Gitlitz BJ, Tso CL, Acres B, Squiban P, Ross ME, Belldegrun AS, Figlin RA: 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. 2004, 27: 240-253. 10.1097/00002371-200405000-00009.CrossRefPubMed
11.
Bu D, Domenech N, Lewis J, Taylor-Papadimitriou J, Finn OJ: Recombinant vaccinia mucin vector: in vitro analysis of expression of tumor-associated epitopes for antibody and human cytotoxic T-cell recognition. J Immunother. 1993, 14: 127-135. 10.1097/00002371-199308000-00008.CrossRef
12.
Balloul JM, Acres RB, Geist M, Dott K, Stefani L, Schmitt D, Drillien R, Spehner D, McKenzie I, Xing PX: Recombinant MUC 1 vaccinia virus: a potential vector for immunotherapy of breast cancer. Cell Mol Biol (Noisy-le-grand). 1994, 40 (Suppl 1): 49-59.
13.
Akagi J, Nakagawa K, Egami H, Ogawa M: Induction of HLA-unrestricted and HLA-class-II-restricted cytotoxic T lymphocytes against MUC-1 from patients with colorectal carcinomas using recombinant MUC-1 vaccinia virus. Cancer Immunol Immunother. 1998, 47: 21-31. 10.1007/s002620050500.CrossRefPubMed
14.
Hodge JW, McLaughlin JP, Kantor JA, Schlom J: Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses. Vaccine. 1997, 15: 759-768. 10.1016/S0264-410X(96)00238-1.CrossRefPubMed
15.
Zhu MZ, Marshall J, Cole D, Schlom J, Tsang KY: Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine. Clin Cancer Res. 2000, 6: 24-33.PubMed
16.
Kudo-Saito C, Hodge JW, Kwak H, Kim-Schulze S, Schlom J, Kaufman HL: 4-1BB ligand enhances tumor-specific immunity of poxvirus vaccines. Vaccine. 2006, 24: 4975-4986. 10.1016/j.vaccine.2006.03.042.PubMedCentralCrossRefPubMed
17.
Croft M, Dubey C: Accessory molecule and costimulation requirements for CD4 T cell response. Crit Rev Immunol. 1997, 17: 89-118.CrossRefPubMed
18.
Kaufman HL, Cohen S, Cheung K, DeRaffele G, Mitcham J, Moroziewicz D, Schlom J, Hesdorffer C: Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors. Hum Gene Ther. 2006, 17: 239-244. 10.1089/hum.2006.17.239.CrossRefPubMed
19.
Hodge JW, Greiner JW, Tsang KY, Sabzevari H, Kudo-Saito C, Grosenbach DW, Gulley JL, Arlen PM, Marshall JL, Panicali D, Schlom J: Costimulatory molecules as adjuvants for immunotherapy. Front Biosci. 2006, 11: 788-803. 10.2741/1837.CrossRefPubMed
20.
Dipaola R, Plante M, Kaufman H, Petrylak D, Israeli R, Lattime E, Manson K, Schuetz T: A Phase I Trial of Pox PSA vaccines (PROSTVAC(R)-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOMtrade mark) in Patients with Prostate Cancer. J Transl Med. 2006, 4: 1-5. 10.1186/1479-5876-4-1.PubMedCentralCrossRefPubMed
21.
Kaufman HL, DeRaffele G, Mitcham J, Moroziewicz D, Cohen SM, Hurst-Wicker KS, Cheung K, Lee DS, Divito J, Voulo M: Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J Clin Invest. 2005, 115: 1903-1912. 10.1172/JCI24624.PubMedCentralCrossRefPubMed
22.
Kaufman HL, Wang W, Manola J, DiPaola RS, Ko YJ, Sweeney C, Whiteside TL, Schlom J, Wilding G, Weiner LM: Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2004, 22: 2122-2132. 10.1200/JCO.2004.08.083.CrossRefPubMed
23.
Shankar P, Schlom J, Hodge J: Enhanced activation of rhesus T cells by vectors endcoding a triad of costimulatory molecules (B7-1, ICAM-1, LFA-3). Vaccine. 2002, 20: 744-755. 10.1016/S0264-410X(01)00409-1.CrossRef
24.
Hodge J, Sabzevari H, Yafal A, Gritz L, Lorenz M, Schlom J: A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res. 1999, 59: 5800-5807.PubMed
25.
Hodge J, Abrams S, Schlom J, Kantor J: Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res. 1994, 54: 5552-5555.PubMed
26.
Shankar P, Schlom J, Hodge JW: Enhanced activation of rhesus T cells by vectors encoding a triad of costimulatory molecules (B7-1, ICAM-1, LFA-3). Vaccine. 2001, 20: 744-755. 10.1016/S0264-410X(01)00409-1.CrossRefPubMed
27.
Wang R, Epstein J, Baraceros FM, Gorak EJ, Charoenvit Y, Carucci DJ, Hedstrom RC, Rahardjo N, Gay T, Hobart P: Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine. Proc Natl Acad Sci USA. 2001, 98: 10817-10822. 10.1073/pnas.181123498.PubMedCentralCrossRefPubMed
28.
Sedegah M, Jones TR, Kaur M, Hedstrom R, Hobart P, Tine JA, Hoffman SL: Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine. Proc Natl Acad Sci USA. 1998, 95: 7648-7653. 10.1073/pnas.95.13.7648.PubMedCentralCrossRefPubMed
29.
Hodge JW, Poole DJ, Aarts WM, Gomez Yafal A, Gritz L, Schlom J: Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses. Cancer Res. 2003, 63: 7942-7949.PubMed
30.
Santra S, Sun Y, Parvani JG, Philippon V, Wyand MS, Manson K, Gomez-Yafal A, Mazzara G, Panicali D, Markham PD: Heterologous Prime/Boost Immunization of Rhesus Monkeys by Using Diverse Poxvirus Vectors. J Virol. 2007, 81: 8563-8570. 10.1128/JVI.00744-07.PubMedCentralCrossRefPubMed
31.
Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC: Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity. Proc Natl Acad Sci USA. 1993, 90: 3539-3543. 10.1073/pnas.90.8.3539.PubMedCentralCrossRefPubMed
32.
Morrissey PJ, Bressler L, Park LS, Alpert A, Gillis S: Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells. J Immunol. 1987, 139: 1113-1119.PubMed
33.
Conry RM, Allen KO, Lee S-w, Moore SE, Shaw DR, LoBuglio AF: Human Autoantibodies to Carcinoembryonic Antigen (CEA) Induced by a Vaccinia-CEA Vaccine. Clin Cancer Res. 2000, 6: 34-41.PubMed
34.
Manson K, Dolan K, Marshall J: A novel non-HLA restricted cellular immune assay for monitoring patient response to targeted immunotherapeutics. Proc Am Soc Clin Oncol. 2006, 24 (Suppl 18S): 2567-
35.
Eichner M: Analysis of Historical Data Suggests Long-lasting Protective Effects of Smallpox Vaccination. Am J Epidemiol. 2003, 158: 717-723. 10.1093/aje/kwg225.CrossRefPubMed
36.
Slierendregt BL, van Noort JT, Bakas RM, Otting N, Jonker M, Bontrop RE: Evolutionary stability of transspecies major histocompatibility complex class II DRB lineages in humans and rhesus monkeys. Hum Immunol. 1992, 35: 29-39. 10.1016/0198-8859(92)90092-2.CrossRefPubMed
37.
Otting N, Bontrop RE: Evolution of the major histocompatibility complex DPA1 locus in primates. Hum Immunol. 1995, 42: 184-187. 10.1016/0198-8859(94)00095-8.CrossRefPubMed
38.
Geluk A, Elferink DG, Slierendregt BL, van Meijgaarden KE, de Vries RR, Ottenhoff TH, Bontrop RE: Evolutionary conservation of major histocompatibility complex-DR/peptide/T cell interactions in primates. J Exp Med. 1993, 177: 979-987. 10.1084/jem.177.4.979.CrossRefPubMed
39.
't Hart BA, Bauer J, Brok HP, Amor S: Non-human primate models of experimental autoimmune encephalomyelitis: Variations on a theme. J Neuroimmunol. 2005, 168: 1-12. 10.1016/j.jneuroim.2005.05.017.CrossRefPubMed
40.
Marshall JL, Hoyer RJ, Toomey MA, Faraguna K, Chang P, Richmond E, Pedicano JE, Gehan E, Peck RA, Arlen P: Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol. 2000, 18: 3964-3973.PubMed
41.
Chan A, Lockhart D, von Bernstorff W, Spanjaard R, Joo H-G, Eberlein T, Goedegebuure P: Soluble MUC1 secreted by human epithelial cancer cells mediates immune suppression by blocking T-cell activation. Int J Cancer. 1999, 82: 721-726. 10.1002/(SICI)1097-0215(19990827)82:5<721::AID-IJC16>3.0.CO;2-N.CrossRefPubMed
42.
Ungefroren H, Voss M, Bernstorff WV, Schmid A, Kremer B, Kalthoff H: Immunological Escape Mechanisms in Pancreatic Carcinoma. Ann NY Acad Sci. 1999, 880: 243-251. 10.1111/j.1749-6632.1999.tb09529.x.CrossRefPubMed
43.
Feng Y, Wang D, Yuan R, Parker CM, Farber DL, Hadley GA: CD103 Expression Is Required for Destruction of Pancreatic Islet Allografts by CD8+ T Cells. J Exp Med. 2002, 196: 877-886. 10.1084/jem.20020178.PubMedCentralCrossRefPubMed
44.
Gaspar NJ, Li L, Kapoun AM, Medicherla S, Reddy M, Li G, O'Young G, Quon D, Henson M, Damm DL: Inhibition of Transforming Growth Factor beta Signaling Reduces Pancreatic Adenocarcinoma Growth and Invasiveness. Mol Pharmacol. 2007, 72: 152-161. 10.1124/mol.106.029025.CrossRefPubMed
45.
French JJ, Cresswell J, Wong W, Seymour K, Charnley RM, Kirby J: T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?. Br J Cancer. 2002, 87: 1034-1041. 10.1038/sj.bjc.6600597.PubMedCentralCrossRefPubMed
46.
Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower RC: Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation. J Clin Oncol. 2001, 19: 145-156.PubMed
47.
Ryschich E, Notzel T, Hinz U, Autschbach F, Ferguson J, Simon I, Weitz J, Frohlich B, Klar E, Buchler MW, Schmidt J: Control of T-cell-mediated immune response by HLA class I in human pancreatic carcinoma. Clin Cancer Res. 2005, 11: 498-504.PubMed
48.
Marshall JL, Gulley JL, Arlen PM, Beetham PK, Tsang K-Y, Slack R, Hodge JW, Doren S, Grosenbach DW, Hwang J: Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM Alone and Sequentially With Vaccinia-CEA(6D)-TRICOM, With and Without Granulocyte-Macrophage Colony-Stimulating Factor, in Patients With Carcinoembryonic Antigen-Expressing Carcinomas. J Clin Oncol. 2005, 23: 720-731. 10.1200/JCO.2005.10.206.CrossRefPubMed
Metadata
Title
Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer
Authors
Howard L Kaufman
Seunghee Kim-Schulze
Kelledy Manson
Gail DeRaffele
Josephine Mitcham
Kang Seok Seo
Dae Won Kim
John Marshall
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2007
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-5-60

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Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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