Gene therapy with recombinant adenovirus vectors: evaluation of the host immune response

Christ, Marielle; Lusky, Monika; Stoeckel, Fabienne; Dreyer, Dominique; Dieterlé, A; Michou, Anne-Isabelle; Pavirani, Andréa; Mehtali, Majid

doi:10.1016/s0165-2478(97)00049-7

Cited by 128 publications

(90 citation statements)

References 30 publications

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“…The development of neutralising antibodies against adenoviral antibodies following injection of viral vectors is a major problem in recombinant adenoviral immunotherapy (Christ et al, 1997). This problem can be avoided by in vitro transduction of DCs.…”

Section: Discussionmentioning

confidence: 99%

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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Transduction of recombinant adenovirus into dendritic cells (DCs) is a promising new tool for cancer vaccine development. Here, we report that an adenovirus vector carrying hepatocellular carcinoma (HCC) antigen HCA661 and infected into DCs generates T-cell immunity against hepatoma cells. HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of an HCC patient. We constructed a recombinant adenovirus expressing the full-length cDNA of HCA661 gene and then transduced immature DCs, which had been generated with GM-CSF and IL-4 from peripheral blood mononuclear cell of HLA-A2 þ healthy donors. The resulting adenovirus-transduced DCs differentiated in the presence of monocyte-conditioned medium and poly [I] : poly [C], expressing the surface markers of mature DCs, including CD83, CD80, CD86 and HLA-DR. After maturation, the transduced DCs transcribed HCA661 mRNA and were able to prime the naïve T cells to become cytotoxic T lymphocytes (CTLs). Intracellular flow cytometry and enzyme-linked immunospot assay showed that these CTLs were able to target a hepatoma cell line, HepG2, which is HLA-A2 and HCA661 positive. In summary, we found that this recombinant adenovirus can help to induce DC maturation and these mature DCs can activate T cells to target hepatoma cells. Therefore, this recombinant adenovirus may have potential for use in liver cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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“…[54][55][56][57][58] FK506 has been used previously to prevent the rejection of transgene products brought in recipient animals by cellular or viral vectors. [37][38][39][40][41][42][43][44] Our present results indicate that the specific immune reactions are blocked by the permanent or discontinuous administration of the FK506 immunosuppressant. The protection, however, fades away and the number of ␤-gal-positive fibers decreases with time after termination of FK506.…”

Section: Figure 7 Lack Of Persistence Of Transduced Fibers In An Acutmentioning

confidence: 91%

“…For instance, FK506 blocked the cellular and humoral rejection of transgene products in cell-or virus-mediated gene transfer in mice. [38][39][40][41][42][43][44] Therefore, in the present study, FK506 was used to prevent the rejection of transduced muscle fibers by the mature, adult immune system of the recipient mice. As expected, the daily immunosuppression of animals following transduction led to the persistency of a high percentage of labeled fibers for several weeks in wild-type mice.…”

Section: Requirement Of Immunosuppression For Long-term Transgene Expmentioning

confidence: 99%

Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular dystrophies

Vilquin

Kennel²,

Paturneau-Jouas

et al. 2001

Gene Ther

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The electrotransfer of naked DNA has recently been adapted to the transduction of skeletal muscle fibers. We investigated the short-and long-term efficacy of this methodology in wild-type animals and in mouse models of congenital muscular dystrophy (dy/dy, dy 2J /dy 2J ), or Duchenne muscular dystrophy (mdx/mdx). Using a reporter construct, the short-term efficacy of fiber transduction reached 40% and was similar in wild-type, dy/dy and dy 2J /dy 2J animals, indicating that ongoing muscle fibrosis was not a major obstacle to the electrotransfer-mediated gene transfer. Although the complete rejection of transduced fibers was observed within 3 weeks in the absence of immunosuppression, the persistency was prolonged over 10 weeks when transient or continuous immunosuppressive regimens were used. Using

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“…One of the limitations imposed onto gene therapy is the immune response directed against vector and/or transgene product. [1][2][3][4] While beneficial for the development of recombinant vaccines against infectious agents 5,6 and tumor cells, 7,8 it significantly impedes the development of those gene-therapy approaches where persistent expression of the transgenes encoding neoantigens is required. Long-term humoral and cellular immunity against several viral-vector systems prevails in a large part of the population, or may be induced upon the first vector administration.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16] This requires prior activation of CD4 þ T cells. 1,[16][17][18][19][20][21][22][23] Also in primates a CTL response directed against the transgene product has been shown to occur. 24,25 In a clinical trial aiming at inducing a graft versus leukemia response, eight of 24 treated patients developed a specific cytotoxic CD8 þ T-cell-mediated immune response against the cells genetically engineered to express the Herpes Simplex Virus 1 (HSV1) thymidine-kinase (TK) gene.…”

Section: Introductionmentioning

confidence: 99%

Creation of immune ‘stealth’ genes for gene therapy through fusion with the Gly-Ala repeat of EBNA-1

et al. 2003

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A major obstacle in gene-therapy protocols is T-cellmediated destruction of transgene-expressing cells. Therefore new approaches are needed to prevent rapid clearance of transduced cells. We exploited the Gly-Ala repeat (GAr) domain of the Epstein-Barr virus nuclear antigen-1, since the GAr prevents cytotoxic T-lymphocyte-epitope generation. Here we show that three different enzymes (viz. the E. coli LacZ gene encoded b-galactosidase, firefly luciferase, and HSV1 thymidine kinase) fused with the GAr retained their function. Moreover, linking GAr with b-galactosidase successfully prevented recognition of GAr-LacZ-expressing cells by b-galactosidase-specific CTL. Nonetheless, vaccination with a GAr-LacZ adenovirus or with an allogeneic cell line expressing GAr-LacZ resulted in the induction of b-galspecific CTL. This demonstrates that the GAr domain does not inhibit crosspresentation of antigens, but only affects breakdown of endogenously synthesized proteins. These data demonstrate how the GAr domain can be exploited to create immuno'stealth' genes by hiding transgene products from CTL-mediated immune attack.

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Gene therapy with recombinant adenovirus vectors: evaluation of the host immune response

Cited by 128 publications

References 30 publications

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular dystrophies

Creation of immune ‘stealth’ genes for gene therapy through fusion with the Gly-Ala repeat of EBNA-1

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