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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.01.2013 | Original Paper

Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC

verfasst von: Mervat El Ansary, Sherif Mogawer, Samah Abd Elhamid, Sahr Alwakil, Fatma Aboelkasem, Hatem El Sabaawy, Olfat Abdelhalim

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2013

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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.

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 12:2817–2825PubMedCrossRef

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 28:129–135PubMedCrossRef

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 63:12–17PubMed

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 95:9482–9487PubMedCrossRef

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 26:369–379PubMedCrossRef

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 52:155–161PubMed

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 74:69–80CrossRef

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

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

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

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 28:496–504PubMedCrossRef

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

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 59:56–58PubMed

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 198:1023–1034PubMedCrossRef

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

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

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

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 49:124–132PubMedCrossRef

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

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

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 190:1669–1678PubMedCrossRef

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 11:5614–5620PubMed

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 238:61–66PubMedCrossRef

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):450–456PubMedCrossRef

Titel: Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC
verfasst von: Mervat El Ansary
Sherif Mogawer
Samah Abd Elhamid
Sahr Alwakil
Fatma Aboelkasem
Hatem El Sabaawy
Olfat Abdelhalim
Publikationsdatum: 01.01.2013
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-012-1298-8

Springer Medizin

Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC