Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 Mar;92(3):321–327. doi: 10.1111/j.1349-7006.2001.tb01098.x

Efficient Gene Transduction by RGB‐fiber Modified Recombinant Adenovirus into Dendritic Cells

Rumiko Asada‐Mikami 1,4, Yuji Heike 5,, Sachiyo Kanai 1, Masato Azuma 1, Kazuo Shirakawa 1, Yoichi Takaue 3, Victor Krasnykh 6, David T Curiel 6, Masaaki Terada 2, Tatsuo Abe 4, Hiro Wakasugi 1,
PMCID: PMC5926705  PMID: 11267943

Abstract

Dendritic cells (DC) are important antigen‐presenting cells in the development of an anti‐tumor T cell response. To extend the range of current immuno/gene therapies, we tested luciferase‐expressing RGD‐adenovirus (Ad) (Ad5lucRGD)‐mediated transduction into DC. Phenotypically characterized DC were generated from peripheral blood CD14+ cells by incubation with granulocyte‐macrophage colony‐stimulating factor, interleukin‐4 and tumor necrosis factor a. On the 7th day of culture, the cells became mature DC with a CD1a+, CD11c+, CD80+, CD83+, CD86+, human leukocyte antigen (HLA)‐DR+, CD14 phenotype. The expression of (α,β3 integrin was enhanced on day 3 and returned to the basal level on day 7. We then compared the transduction efficiency of an AdSlucRGD system to that using conventional Ad, in cells harvested on days 1, 3 and 7 of culture. Luciferase activity was negligible in AdCMVLuc, but remarkable in cells processed with Ad5lucRGD. Activity was maximal in cells that had been cultured for 3 days. Recombinant Ad5 fiber knob protein blocked AdCMVLuc‐ and Ad5lucRGD‐mediated gene transduction by 90% and 20%, respectively. Surface markers and cytokine production were not affected by Ad5lucRGD‐mediated transduction.

Keywords: Adenoviridae, Gene tranfer, Dendritic cell, Integrins, Coxsackie, adenovirus

Full Text

The Full Text of this article is available as a PDF (773.2 KB).

References

  • 1.Hart , D. N . Dendritic cells: unique leukocyte populations which control the primary immune response . Blood , 90 , 1651 – 1658 ( 1997. ). [PubMed] [Google Scholar]
  • 2.Schott , M. , Feldkamp , J. , Schattenberg , D. , Seissler , J . and Scherbaum , W. A . Dendritic cell immuno‐therapy in disseminated parathyroid carcinoma . Lancet , 353 , 1188 – 1189 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 3.Osman , Y. , Takahashi , M. , Zheng , Z. , Koike , T. , Toba , K. , Liu , A. , Furukawa , T. , Aoki , S . and Aizawa , Y . Generation of bcr‐abl specific cytotoxic T‐lymphocytes by using dendritic cells pulsed with bcr‐abl (β3α2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients . Leukemia , 13 , 166 – 174 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 4.Movassagh , M. , Baillou , C. , Cosset , F. L. , Klatzmann , D. , Guigon , M . and Lemoine , F. M . High level of retrovirus‐mediated gene transfer into dendritic cells derived from cord blood and mobilized peripheral blood CD34+ cells . Hum. Gene Ther. , 10175 – 187 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 5.Timmerman , J. M . and Levy , R . Dendritic cell vaccines for cancer immunotherapy . Annu. Rev. Med. , 50 , 507 – 529 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 6.Bilbao , G. , Gomez‐Navarro , J . and Curiel , D. T . Targeted adenoviral vectors for cancer gene therapy . Adv. Exp. Med. BioL , 451 , 365 – 374 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 7.Arthur , J. F. , Butterfield , L. H. , Roth , M. D. , Bui , L. A. , Kiertscher , S. M. , Lau , R. , Dubinett , S. , Glaspy , J. , Mcbride , W. H . and Economou , J. S . A comparison of gene transfer methods in human dendritic cells . Cancer Gene Ther. , 4 , 17 – 25 ( 1997. ). [PubMed] [Google Scholar]
  • 8.Bergelson , J. M. , Cunningham , J. A. , Drogueit , G. , Kurt‐Jones , E. A. , Krithivas , A. , Hong , J. S. , Horwitz , M. S. , Crowell , R. L . and Finberg , R. W . Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5 . Science , 275 , 1320 – 1323 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 9.Bergelson , J. M. , Krithivas , A. , Celi , L. , Droguett , G. , Horwitz , M. S. , Wickham , T. , Crowell , R. L . and Finberg , R. W . The murine CAR homolog is a receptor for coxsackie viruses and adenoviruses . J. Virol. , 72 , 415 – 419 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Tomko , R. P. , Xu , R. and Philipson , L . HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses . Proc. Natl. Acad. Set. USA , 94 , 3352 – 3356 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Dmitriev , L , Krasnykh , V. , Miller , C. R. , Wang , M. , Kashentseva , E. , Mikheeva , G. , Belousova , N . and Curiel , D. T . An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor‐independent cell entry mechanism . J. Virol , 72 , 9706 – 9713 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Pickl , W. F. , Majdic , O. , Kohl , P. , Stockl , J. , Riedl , E. , Scheinecker , C. , Bello‐Fernandez , C . and Knapp , W . Molecular and functional characteristics of dendritic cells generated from highly purified CD14+ peripheral blood monocytes . J. Immunol. , 157 , 3850 – 3859 ( 1996. ). [PubMed] [Google Scholar]
  • 13.Krasnykh , V. , Dmitriev , L , Mikheeva , G. , Miller , C. R. , Belousova , N . and Curiel , D. T . Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob . J. Virol. , 72 , 1844 – 1852 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kanegae , Y. , Makimura , M . and Saito , I . A simple and efficient method for purification of infectious recombinant adenovirus . Jpn. J. Med. Sci. Biol , 41 , 157 – 166 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 15.Zhou , L. J . and Tedder , T. F . CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells . Proc. Natl. Acad. Sci. USA , 93 , 2588 – 2592 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Wickham , T. J. , Lee , G. M. , Titus , J. A. , Sconocchia , G. , Bakacs , T. , Kovesdi , I . and Segal , D. M . Increased in vivo gene transfer by adenovirus vectors containing chimeric fiber protein . J. Virol. , 71 , 8221 – 8229 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Miltenyi , S. , Muller , W. , Weichel , W . and Radbruch , A . High gradient magnetic cell separation with MACS . Cytometry , 11 , 231 – 238 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 18.von Seggern , D. J. , Kehler , J. , Endo , R. I . and Nemerow , G. R . Complementation of a fiber mutant adenovirus by packaging cell lines stably expressing the adenovirus type 5 fiber protein . J. Gen. Virol , 79 , 1461 – 1468 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 19.Banchereau , J . and Steinman , R. M . Dendritic cells and the control of immunity . Nature , 392 , 245 – 252 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 20.Cella , M. , Sallusto , F . and Lanzavecchia , A . Origin, maturation and antigen presenting function of dendritic cells . Curr. Opin. Immunol , 9 , 10 – 16 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 21.Girolomoni , G . and Riccardi‐Castagnoli , P . Dendritic cells hold promise for immunotherapy . Immunol. Today , 18 , 782 – 787 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 22.Austyn , J. M . Dendritic cellsCurr. Opin. Hematol , 5 , 3 – 15 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 23.Schuler , G . and Steinman , R. M . Dendritic cells as adjuvants for immune‐mediated resistance to tumors . J. Exp. Med. , 186 , 1183 – 1187 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Tuting , T. , Zorina , T. , Ma , D. I. , Wilson , C. C. , de Cesare , C. M. , de Leo , A. B. , Lotze , M. T . and Storkus , W. J . Development of dendritic cell‐based genetic vaccines for cancer . Adv. Exp. Med. BioL , 417 , 511 – 518 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 25.Nestle , F. O. , Alijagic , S. , Gilliet , M. , Sun , Y. , Grabbe , S. , Dummer , R. , Burg , G . and Schadendorf , D . Vaccination of melanoma patients with peptide‐ or tumor lysate‐pulsed dendritic cells . Nat. Med. , 4 , 328 – 332 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 26.Westermann , J. , Aicher , A. , Qin , Z. , Cayeux , Z. , Daemen , K. , Blankenstein , T. , Dorken , B . and Pezzutto , A . Retrovi‐ral interleukin‐7 gene transfer into human dendritic cells enhances T cell activation . Gene Ther. , 5 , 264 – 271 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 27.Simons , J. W . and Mikhak , B . Ex‐vivo gene therapy using cytokine‐transduced tumor vaccines: molecular and clinical pharmacology . Semin. Oncol , 25 , 661 – 676 ( 1998. ). [PubMed] [Google Scholar]
  • 28.Fernandez , N. , Duffour , M. T. , Perricadet , M. , Lotze , M. T. , Tursz , T . and Zitvogel , L . Active specific T‐cell‐based immunotherapy for cancer: nucleic acids, peptides, whole native proteins, recombinant viruses, with dendritic cell adjuvants or whole tumor cell‐based vaccines. Principles and future prospects . Cytokines Cell. Mol. Ther. , 4 , 53 – 65 ( 1998. ). [PubMed] [Google Scholar]
  • 29.Butter‐field , L. H. , Jilani , S. M. , Chakraborty , N. G. , Bui , L. A. , Ribas , A. , Dissette , V. B. , Lau , R. , Gamradt , S. C. , Glaspy , J. A. , McBride , W. H. , Mukherji , B . and Economou , J. S . Generation of melanoma‐specific cyto‐toxic T lymphocytes by dendritic cells transduced with a MART‐1 . J. Immunol. , 161 , 5607 – 5613 ( 1998. ). [PubMed] [Google Scholar]
  • 30.Huang , S. , Kamata , T. , Takada , Y. , Ruggeri , Z. M . and Nemerow , G. R . Adenovirus interaction with distinct inte‐grins mediates separate events in cell entry and gene delivery to hematopoietic cells . J. Virol. , 70 , 4502 – 4508 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Albert , M. L. , Sauter , B . and Bhardwaj , N . Dendritic cells acquire antigen from apoptotic cells and induce class I‐restricted CTLs . Nature , 392 , 86 – 89 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 32.Inaba , K. , Turley , S. , Yamaide , F. , Lyoda , T. , Mahnke , K. , Inaba , M. , Pack , M. , Subklewe , M. , Sauter , B. , Sheff , D. , Albert , M. , Bhardwaj , N. , Mellman , I . and Steinman , R. M . Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells . J. Exp. Med. , 188 , 2163 – 2173 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Chang , J. W. , Peng , M. , Vaquerano , J. E. , Zhou , Y. M. , Clinton , R. A. , Hyun , W. C. , Giedlin , M. A . and Leong , S. P . Induction of Thl response by dendritic cells pulsed with autologous melanoma apoptotic bodies . Anticancer Res. , 20 , 1329 – 1336 ( 2000. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES