Early immune response against retrovirally transduced herpes simplex virus thymidine kinase-expressing gene-modified T cells coinfused with a T cell-depleted marrow graft: an altered immune response? - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Human Gene Therapy Année : 2008

Early immune response against retrovirally transduced herpes simplex virus thymidine kinase-expressing gene-modified T cells coinfused with a T cell-depleted marrow graft: an altered immune response?

Jean-Yves Cahn
  • Fonction : Auteur

Résumé

Administration of herpes simplex thymidine kinase (HSV-tk)-expressing, gene-modified T cells (GMCs) with T cell-depleted bone marrow transplantation (TCD-BMT) can allow modulation of posttransplantation alloreactivity. Twelve patients received 2 x 10(5) to 2 x 10(6) CD3+ donor GMCs per kilogram with HLA-identical sibling TCD-BMT. Despite extensive T cell depletion of bone marrow, an intensive conditioning regimen, and immunosuppressive graft-versus-host disease (GvHD) prophylaxis, infusion at the time of TCD-BMT of this low number of GMCs sufficed to induce a rapid GMC-specific immune response, as detected by interferon- enzyme- linked immunospot assay in six of eight patients, preferentially targeting HSV-tk. Maximal responses were reached early (median time, 49 [35-68] days post-BMT), with a subsequent rapid and significant decrease in five of six evaluable patients. Immune responses were negatively correlated with the maximal circulating GMC counts. However, such immune response did not result in the elimination of circulating GMCs and was not associated with measurable ex vivo cytotoxic activity against GMCs. Furthermore, alloreactive GMCs still could induce GCV-sensitive GvHD in one patient despite an ongoing immune response. Overall, infusion of HSV-tk-expressing GMCs at the time of BMT results in an early immune response. Such immune response may be altered and may not prevent persistent GCV-sensitive alloreactivity.

Domaines

Immunologie
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Dates et versions

inserm-00483370 , version 1 (14-05-2010)

Identifiants

  • HAL Id : inserm-00483370 , version 1
  • PUBMED : 18810797

Citer

Patricia Mercier-Letondal, Marina Deschamps, Delphine Sauce, Jean-Marie Certoux, Noël N. Milpied, et al.. Early immune response against retrovirally transduced herpes simplex virus thymidine kinase-expressing gene-modified T cells coinfused with a T cell-depleted marrow graft: an altered immune response?. Human Gene Therapy, 2008, 19 (9), pp.937-50. ⟨inserm-00483370⟩
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