HSV amplicon-mediated delivery of LIGHT enhances the antigen-presenting capacity of chronic lymphocytic leukemia

Khaled A. Tolba, William J. Bowers, David J. Eling, Ann E. Casey, Thomas J. Kipps, Howard J. Federoff, Joseph D. Rosenblatt

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Chronic lymphocytic leukemia (CLL) is a B lymphocyte malignancy that remains a largely incurable disease. CLL B cells possess the ability to process and present tumor antigens but lack expression of costimulatory molecules, rendering them inefficient effectors of T-cell activation. We previously demonstrated that helper virus-free preparations of herpes simplex virus (HSV) amplicon vectors encoding CD40L efficiently transduce CLL B cells and render them capable of eliciting specific anti-tumor T-cell responses. LIGHT (TNFSF14), a member of the tumor necrosis factor (TNF) superfamily, efficiently activates both T cells and antigen-presenting cells (APCs). We employed an HSV amplicon vector expressing human LIGHT (hf-HSV-LIGHT) to transcluce CLL B cells and compared the immunomodulatory function and T-cell activation induced by hf-HSV. LIGHT transduction to that observed with a CD40L-expressing HSV amplicon (hf-HSV-CD40L). hf-HSV-LIGHT transcluction induced expression of endogenous B7.1, B7.2, and ICAM.1 on CLL cells, albeit to a lesser degree than that observed in response to transduction with hf-HSV-CD40L. hf-HSV-LIGHT enhanced the antigen-presenting capacity of CLL B cells, as measured by induction of T-cell proliferation in an allogeneic mixed lymphocyte tumor reaction. Finally, hf-HSV-LIGHT-transduced CLL B cells successfully stimulated the outgrowth of autologous cytotoxic T-lymphocytes in vitro. In aggregate, these data suggest that hf-HSV-LIGHT transduction may be useful for induction of immune responses to CLL and other B-cell lymphoid malignancies.

Original languageEnglish (US)
Pages (from-to)455-463
Number of pages9
JournalMolecular Therapy
Volume6
Issue number4
DOIs
StatePublished - Oct 1 2002

Keywords

  • Cancer immunotherapy
  • CD40L
  • CLL
  • HSV amplicon
  • LIGHT

ASJC Scopus subject areas

  • Molecular Biology

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