Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Tolba, K.A. et al.

Tolba, Bowers, Eling, Casey, Kipps, Federoff, Rosenblatt,

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

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 transduce 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 transduction 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.[1]

References

HSV amplicon-mediated delivery of LIGHT enhances the antigen-presenting capacity of chronic lymphocytic leukemia. Tolba, K.A., Bowers, W.J., Eling, D.J., Casey, A.E., Kipps, T.J., Federoff, H.J., Rosenblatt, J.D. Mol. Ther. (2002) [Pubmed]

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