BACKGROUND: B lymphoblastoid cell-lines (BLCL), generated by exposure of PBMC to a laboratory strain of EBV, are commonly utilized in the preparation of T cells used for immunotherapy. Although most B cells are latently infected, BLCL contain a subset of cells that harbor infectious virus, which could be released into the infusion product during preparation. To reduce this known risk, laboratories have pretreated BLCL for > or = 14 days with 100 microM @entity1033 ( @entity3073 ), an inhibitor of viral DNA polymerase, prior to use. We tested the effectiveness of @entity3073 in preventing the release of infectious virus from irradiated fresh and previously frozen BLCL, and compared its effects with those of @entity4540 (GCV). METHODS: BLCL were grown for 14 days in medium containing various doses of @entity3073 or GCV, washed, irradiated, and tested for the presence of infectious virus in co-culture assays with cord blood mononuclear cells(CBMC) (21 CBMC to BLCL). B-cell transformation was assessed at 3-4 weeks of culture. RESULTS: Both fresh and previously frozen BLCL released infectious virus, which transformed nearly all (92%) of CBMC co-cultures (n = 52). Transformation was not prevented by treatment with 100 microM @entity3073 (88%, n = 52). Increasing the @entity3073 dose to 200 microM (or 50 microg/mL) still allowed transformation in 4/9 (44%) cultures, while this and higher doses severely reduced the proliferation rate of the BLCL during @entity3073 exposure. Infectious virus release was detectable within 1 day of @entity3073 removal and BLCL irradiation. In contrast, GCV was able to prevent infectious virus release in 12/12 co-cultures at a concentration (15 microM) that only modestly reduced BLCL growth. DISCUSSION: These results indicate that GCV is more effective at preventing release of infectious EBV from irradiated BLCL than @entity3073 at concentrations that do not severely inhibit B-cell growth.

Suppression of EBV release from irradiated B lymphoblastoid cell-lines: superior activity of XXXX compared with @entity1033 .

@entity1033 :: ('MESH:D000212', 'Chemical') :: ['acyclovir'] @entity4540 :: ('MESH:D015774', 'Chemical') :: ['ganciclovir'] @entity3073 :: ('CHEBI:28496', 'Chemical') :: ['ACV']
@entity4540 :: (MESH:D015774,Chemical) :: ['ganciclovir']
