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Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Dendritic cells (DCs) could be used as potential cellular adjuvant for the production of specific tumor vaccines.

Objectives

Our study was aimed to evaluate the safety and efficacy of autologous pulsed DC vaccine in advanced hepatocellular carcinoma (HCC) patients in comparison with supportive treatment.

Methods

Thirty patients with advanced HCC not suitable for radical or loco-regional therapies were enrolled. Patients were divided into 2 groups, group I consisted of 15 patients received I.D vaccination with mature autologous DCs pulsed ex vivo with a liver tumor cell line lysate. Group II (control group, no. 15) received supportive treatment. One hundred and 4 ml of venous blood were obtained from each patient to generate DCs. DCs were identified by CD80, CD83, CD86 and HLA-DR expressions using flow cytometry. Follow up at 3, and 6 months post injection by clinical, radiological and laboratory assessment was done.

Results

Improvement in overall survival was observed. Partial radiological response was obtained in 2 patients (13.3 %), stable course in 9 patients (60 %) and 4 patients (26.7 %) showed progressive disease (died at 4 months post-injection). Both CD8+ T cells and serum interferon gamma were elevated after DCs injection.

Conclusion

Autologous DC vaccination in advanced HCC patients is safe and well tolerate.

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Abbreviations

AFP:

Alfa feto protein

BM:

Bone marrow

CTL:

Cytotoxic T-lymphocyte

DC:

Dendritic cells

HCC:

Hepatocellular carcinoma

ID:

Intradermal

IFN-γ:

Iterferon gamma

TACE:

Transarterial chemoembolization

TSA:

Tumor-specific antigens

References

  • Butterfield LH, Ribas A, Dissette VB et al (2006) A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin Cancer Res 12:2817–2825

    Article  PubMed  CAS  Google Scholar 

  • 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 28:129–135

    Article  PubMed  Google Scholar 

  • De Vries IJ, Krooshoop DJ, Scharenborg NM et al (2003) Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 63:12–17

    PubMed  Google Scholar 

  • Fields RC, Shimizu K, Mule JJ (1998) Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc Natl Acad Sci USA 95:9482–9487

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Carmona MA, Marten A, Hoffmann P et al (2006) Patient-derived dendritic cells transduced with an a-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells. Liver Int 26:369–379

    Article  PubMed  CAS  Google Scholar 

  • Iwashita Y, Tahara K, Goto S et al (2003) A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Cancer Immunol Immunother 52:155–161

    PubMed  CAS  Google Scholar 

  • Katharina T, Thomas MC, Helena H et al (2003) Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines. J Leukoc Biol 74:69–80

    Article  Google Scholar 

  • Kumagi T, Akbar SM, Horiike N et al (2005) Administration of dendritic cells in cancer nodules in hepatocellular carcinoma. Oncol Rep 14:969–973

    PubMed  Google Scholar 

  • Lechmann M, Berchtold S, Hauber J et al (2003) CD83 on dendritic cells: more than just a marker for maturation. Trends Immunol 23:273–275

    Article  Google Scholar 

  • Lee DH (2010) Dendritic cells-based vaccine and immune monitoring for hepatocellular carcinoma. Korean J Physiol Pharmacol 14:11–14

    Article  PubMed  CAS  Google Scholar 

  • Lee WC, Wang HC, Hung CF et al (2005) Vaccination of advanced hepatocellular carcinoma patients with tumor lysate-pulsed dendritic cells: a clinical trial. J Immunother 28:496–504

    Article  PubMed  Google Scholar 

  • Lilah F, Morris MD, Antoni Ribas MD (2007) Therapeutic cancer vaccines. Surg Oncol Clin N Am 16(4):819–831

    Article  Google Scholar 

  • Morse MA, Coleman RE, Akabani G, Niehaus N, Coleman D, Lyerly HK (1999) Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res 59:56–58

    PubMed  CAS  Google Scholar 

  • Mullins DW, Sheasley SL, Ream RM et al (2003) Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control. J Exp Med 198:1023–1034

    Article  PubMed  CAS  Google Scholar 

  • Nakamoto Y, Kaneko S (2010) Dendritic cell-based immunotherapy for hepatocellular carcinoma. Gan To Kagaku Ryoho 37(3):413–416

    PubMed  Google Scholar 

  • Nestle FO, Alijagic S, Gilliet M et al (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4:328–332

    Article  PubMed  CAS  Google Scholar 

  • Palmer DH, Hussain SA, Johnson PJ (2005) Gene- and immunotherapy for hepatocellular carcinoma. Expert Opin Biol Ther 5:507–523

    Article  PubMed  CAS  Google Scholar 

  • Palmer DH, Midgley RS, Mirza N et al (2009) A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology 49:124–132

    Article  PubMed  Google Scholar 

  • Parkin DM, Bray F, Ferlay J et al (2001) Estimating the world cancer burden: globocan 2000. Int J Cancer 94:153–156

    Article  PubMed  CAS  Google Scholar 

  • Schwartz M, Roayaie S, Konstadoulakis M (2007) Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol 4:424–432

    Article  PubMed  CAS  Google Scholar 

  • Thurner B, Haendle I, Roder C et al (1999) Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 190:1669–1678

    Article  PubMed  CAS  Google Scholar 

  • Wang XH, Qin Y, Hu MH et al (2005) Dendritic cells pulsed with hsp70-peptide complexes derived from human hepatocellular carcinoma induce specific anti-tumor immune responses. World J Gastroenterol 11:5614–5620

    PubMed  CAS  Google Scholar 

  • Zhang L, Zhang H, Liu W et al (2005) Specific antihepatocellular carcinoma T cells generated by dendritic cells pulsed with hepatocellular carcinoma cell line HepG2 total RNA. Cell Immunol 238:61–66

    Article  PubMed  CAS  Google Scholar 

  • Zhou P, Liang P, Dong B et al (2011) Phase I clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma. Cancer Biol Ther 11(5):450–456

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported in part by grants from Kasr Al-Aini Hospital. We also thank El-Ansary private laboratories and our patients for their willing participation in our research.

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Clinical Pathology, Kasr Al-Aini, Cairo University, Cairo, Egypt

    Mervat El Ansary, Samah Abd Elhamid & Hatem El Sabaawy

  2. Department of Hepatology and Gastroenterology, Kasr Al-Aini, Cairo University, Cairo, Egypt

    Sherif Mogawer

  3. Department of Internal Medicine, Kasr Al-Aini, Cairo University, Cairo, Egypt

    Sahr Alwakil

  4. Department of Medical Oncology, NCI, Cairo University, Cairo, Egypt

    Fatma Aboelkasem

  5. Department of Hepatology and Gastroenterology, Al-Salam International Hospital, Cairo, Egypt

    Olfat Abdelhalim

Authors
  1. Mervat El Ansary
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  2. Sherif Mogawer
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  3. Samah Abd Elhamid
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  4. Sahr Alwakil
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  5. Fatma Aboelkasem
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  6. Hatem El Sabaawy
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  7. Olfat Abdelhalim
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Corresponding author

Correspondence to Samah Abd Elhamid.

Additional information

ClinicalTrials.gov number: REC 49-2010.

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El Ansary, M., Mogawer, S., Elhamid, S.A. et al. Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC. J Cancer Res Clin Oncol 139, 39–48 (2013). https://doi.org/10.1007/s00432-012-1298-8

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  • DOI: https://doi.org/10.1007/s00432-012-1298-8

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