Anti-HIV genetic treatment of antigen-specific human CD4 lymphocytes for adoptive immunotherapy of opportunistic infections in AIDS

Manca, Fabrizio; Fenoglio, Daniela; Franchin, Elisa; Saverino, Danièle; Pira, Giuseppina Li; Buffa, Francesca M.; Bignardi, Donatella; Pup, Laura Del; Palù, Giorgio

doi:10.1038/sj.gt.3300539

Cited by 16 publications

(17 citation statements)

References 6 publications

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“…Antigen-specific CD4 lines were obtained from normal and from HIVinfected donors and these lines maintained functional immune properties after transduction. 70,71 Irrespective of the gene being transferred, [72][73][74] GT should protect antigen-specific CD4 lymphocytes in vivo more efficiently than HAART, when drug-resistant HIV strains are present. [32][33][34] For a more effective treatment, however, this immune-genetic approach should be adopted in combination with antiretroviral chemotherapy and/or with IL-2 administration to favor expansion of activated CD4 cells.…”

Section: Figure 1 Consequences Of Selective Infection Of Activated CDmentioning

confidence: 99%

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Genetically modified immunocompetent cells in HIV infection

Palù

Pira²,

Gennari

et al. 2001

Gene Ther

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Even in the era of highly active antiretroviral therapy (HAART), gene therapy (GT) can remain a promising approach for suppressing HIV infection, especially if complemented with other forms of pharmacological and immunological intervention. A large number of vectors and targets have been studied. Here we discuss the potential of genetically treated, antigen-specific immunocompetent cells for adoptive autologous immunotherapy of HIV infection. Cellu-

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Section: Figure 1 Consequences Of Selective Infection Of Activated CDmentioning

confidence: 99%

“…Skewing may occurr as a consequence of in vitro culture 96,97 or when therapeutic genes are artificially introduced. 70 Therefore, monitoring of clonal heterogeneity of antigenspecific T cell lines should be performed according to TCR BV gene family usage and spectrotyping. 98 …”

Section: Clonal Heterogeneity Of Antigen-specific Cd4 T Cellsmentioning

confidence: 99%

Genetically modified immunocompetent cells in HIV infection

Palù

Pira²,

Gennari

et al. 2001

Gene Ther

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“…TCC could provide direct clues about the nature and requirements for antigen processing of complex natural glycoconjugates, such as the mannoproteins, which are major T-cell antigens of this fungus (10,12,27,52). They could also provide direct evidence of immunodominant epitopes of the pathogen and might be useful for immunoreconstitution therapy of some forms of candidiasis (33,51). However, we are unaware of any approach specifically devoted to understanding immune responses in candidiasis by the use of Candida-specific human TCC.…”

mentioning

confidence: 99%

“…Human T-cell lines and T-cell clones (TCC) specific for C. albicans have rarely been generated and described in the literature (29,33), although they could be useful tools in the study of immune responses to Candida. TCC could provide direct clues about the nature and requirements for antigen processing of complex natural glycoconjugates, such as the mannoproteins, which are major T-cell antigens of this fungus (10,12,27,52).…”

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confidence: 99%

Antigenic Properties and Processing Requirements of 65-Kilodalton Mannoprotein, a Major Antigen Target of Anti-CandidaHuman T-Cell Response, as Disclosed by Specific Human T-Cell Clones

et al. 2001

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T-cell-mediated immunity is known to play a central role in the host response to Candida albicans. T-cell clones are useful tools for the exact identification of fungal T-cell epitopes and the processing requirements of C. albicans antigens. We isolated human T-cell clones from an HLA-DRB1*1101 healthy donor by using an antigenic extract (MP-F2) of the fungus. Specific clones were T-cell receptor ␣/␤ and CD4 ؉ /CD8 ؊ and showed a T-helper type 1 cytokine profile (production of gamma interferon and not interleukin-4). The large majority of these clones recognized both the natural (highly glycosylated) and the recombinant (nonglycosylated) 65-kDa mannoprotein (MP65), an MP-F2 minor constituent that was confirmed to be an immunodominant antigen of the human T-cell response. Surprisingly, most of the clones recognized two synthetic peptides of different MP65 regions. However, the peptides shared the amino acid motif IXSXIXXL, which may be envisaged as a motif sequence representing the minimal epitope recognized by these clones. Three clones recognized natural and pronase-treated MP65 but did not detect nonglycosylated, recombinant MP65 or the peptides, suggesting a possible role for polysaccharides in T-cell recognition of C. albicans. Finally, lymphoblastoid B-cell lines were efficient antigen-presenting cells (APC) for recombinant MP65 and peptides but failed to present natural, glycosylated antigens, suggesting that nonprofessional APC might be defective in processing highly glycosylated yeast proteins. In conclusion, this study provides the first characterization of C. albicans-specific human T-cell clones and provides new clues for the definition of the cellular immune response against C. albicans.

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“…Our group has previously proposed a new strategy of adoptive immunotherapy based on ex vivo transfer of autologous CD4 T-cell lines, resistant to HIV-1, which recognize specific antigen of HIV-1 and opportunistic infectious agents. [5][6][7] However, the HLA-restricted nature of viral antigen recognition by the T-cell receptor limits the application of adoptive immunotherapy strategies to MHC-matched individuals. To overcome this problem, one promising strategy is to engineer T-lymphocytes genetically to express artificial TCRs that direct cytotoxicity toward viral antigens.…”

Section: Introductionmentioning

confidence: 99%

T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120

et al. 2004

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Immune-based approaches of cell therapy against viral pathogens such as the human immunodeficiency virus type 1 (HIV-1) could be of primary importance for the control of this viral infection. Here, we designed a chimeric cell surface receptor (105TCR) to provide primary human T-lymphocytes with antibody-type specificity for the HIV-1 envelope glycoprotein. This receptor includes the single chain Fv domain of the neutralizing anti-gp120 human monoclonal antibody F105, CD8a hinge and the transmembrane and the cytoplasmic domains of TCRz. Our results show that 105TCR is expressed at the cellular surface and is capable of recognizing the HIV-1 envelope glycoprotein inducing highly efficient effector T-cell responses, including extracellular signal-regulated kinase phosphorylation and cytokine secretion. Moreover, human primary CD8+ T-lymphocytes transduced by oncoretroviral and lentiviral vectors containing the 105TCR gene are able to mediate in vitro-specific cytolysis of envelope-expressing cells and HIV-1-infected CD4+ T-lymphocytes. These findings suggest that 105TCR is particularly suited for in vivo efficacy studies. Gene Therapy (2005) 12, 299-310.

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Anti-HIV genetic treatment of antigen-specific human CD4 lymphocytes for adoptive immunotherapy of opportunistic infections in AIDS

Cited by 16 publications

References 6 publications

Genetically modified immunocompetent cells in HIV infection

Genetically modified immunocompetent cells in HIV infection

Antigenic Properties and Processing Requirements of 65-Kilodalton Mannoprotein, a Major Antigen Target of Anti-CandidaHuman T-Cell Response, as Disclosed by Specific Human T-Cell Clones

T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120

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