Functional reversion of antigen-specific CD8(+) T cells from patients with Hodgkin lymphoma following in vitro stimulation with recombinant polyepitope

Smith, Corey, Cooper, Leanne, Burgess, Melinda, Rist, Michael, Webb, Natasha, Lambley, Eleanore, Tellam, Judy, Marlton, Paula, Seymour, John F., Gandhi, Maher and Khanna, Rajiv (2006) Functional reversion of antigen-specific CD8(+) T cells from patients with Hodgkin lymphoma following in vitro stimulation with recombinant polyepitope. Journal of Immunology, 177 7: 4897-4906.

Author Smith, Corey
Cooper, Leanne
Burgess, Melinda
Rist, Michael
Webb, Natasha
Lambley, Eleanore
Tellam, Judy
Marlton, Paula
Seymour, John F.
Gandhi, Maher
Khanna, Rajiv
Title Functional reversion of antigen-specific CD8(+) T cells from patients with Hodgkin lymphoma following in vitro stimulation with recombinant polyepitope
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2006-10
Sub-type Article (original research)
Volume 177
Issue 7
Start page 4897
End page 4906
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Recent studies on Hodgkin's lymphoma (HL) have indicated that patients with active disease display functional impairment of Ag-specific CD8+ T cells due to expansion of regulatory T cells at sites of disease and in the peripheral blood. Adoptive cellular immunotherapy based on EBV-specific CD8 + T cells has been explored with limited success to date. It has been proposed that improved targeting of these CD8+ T cells toward viral Ags that are expressed in HL may enhance future therapeutic vaccine strategies. In this study, we have developed a novel replication-deficient adenoviral Ag presentation system that is designed to encode glycine alanine repeat-deleted EBV nuclear Ag 1 covalently linked to multiple CD8+ T cell epitopes from latent membrane proteins 1 and 2. A single stimulation of CD8+ T cells from healthy virus carriers, and patients with HL with this adenoviral construct in combination with IL-2, was sufficient to reverse the functional T cell impairment and restored both IFN-γ production and cytolytic function. More importantly, these activated CD8+ T cells responded to tumor cells expressing membrane proteins and recognized novel EBNA1 epitopes. Flow cytometric analysis revealed that a large proportion of T cells expanded from patients with HL were CD62Lhigh and CD27high, and CCR7low, consistent with early to mid effector T cells. These findings provide an important platform for translation of Ag-specific adoptive immunotherapy for the treatment of EBV-associated malignancies such as HL and nasopharyngeal carcinoma.
Keyword Ebv-Associated Malignancies
Reed-Sternberg Cells
Nasopharyngeal Carcinoma
Adoptive Immunotherapy
Lymphoproliferative Disease
Lymphocytes
Effector
Adenovirus
Responses
Epitopes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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