Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment

Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein

“…28,29,32 A recent report described MCD remission in a multiple myeloma patient undergoing treatment with the proteosome inhibitor bortezomib. 33 Finally, herpesvirus-directed treatments using inhibitors of the viral DNA polymerase have shown promise, 34,35 consistent with the involvement of lytic phase replication in MCD; however, as for chemotherapy, the benefits are transient and long-term use is complicated by dose-limiting toxicities of these agents.…”

“…Originally developed to treat herpes simplex virus infection, they also inhibit KSHV in vitro 60,[64][65][66] and have displayed activity against KSHV-associated disease based on reductions in viral oropharyngeal shedding 67,68 and clinical relief of MCD symptoms. 34,35 At the outset, we considered three alternatives: (1) ganciclovir and the immunotoxin might display additive anti-KSHV activities; (2) they might detected on a small subpopulation of induced cells; this pattern was not observed on uninduced cells (data not shown). The mean fluorescent intensity of the entire population of induced cells was 24.9 with mAb 4C3 compared with 8.0 with control IgG1.…”

“…This notion is supported by emerging clinical data for MCD treatment testing the effects of inhibitors of herpes virus replication such as ganciclovir and related agents. In one case study, ganciclovir was associated with reduction in the frequency of active MCD episodes, 34 although in another report cidofovir was found to be ineffective 76 despite its strong anti-KSHV activity in vitro. In a recent pilot study, 35 high-dose zidovudine plus valganciclovir produced significant clinical, biochemical and virologic responses in symptomatic potentiate one another through their differential mechanisms of inhibiting production of infectious virus during the lytic phase of KSHV replication; (3) ganciclovir might compromise immunotoxin activity by suppressing expression of the gpK8.1A target antigen.…”

The pleiotropic effects of Kaposi's sarcoma herpesvirus

“…Two possible mechanisms are frequently discussed. One is based on the observation that the retention of latent viral genomes in dividing cells other than B cells in vitro is very inefficient (see above) and that treatment with inhibitors of the viral DNA polymerase shows some protective effect on the subsequent development of KS [119,120] or MCD [121]. It has therefore been postulated that there is a need for periodic re-infection of endothelial cells by KSHV in order for the virus to persist in vivo [95].…”

KSHV: forgotten but not gone

“…The work extends previous studies suggesting that antivirals can improve MCD patient survival. 8 In their pilot study, Uldrick et al use the ganciclovir prodrug, valganciclovir, together with zidovudine (AZT) to precisely target 2 viral enzymes involved in viral DNA synthesis, the viral phosphotransferase and thymidine kinase, respectively-a first in KSHV oncology. These drugs can potentially be paired with other standard chemotherapies to further improve outcome for this disease that otherwise has a dismal prognosis.…”