Figure 4
Figure 4. Basis for nonresponse: donor-derived EBV-specific T cells did not recognize host origin EBV-LPD (patient 8). (A) HLA type of the stem cell donor (mother), third-party EBV-CTLs donor 1, and third-party EBV-CTL donor 2. (B) HLA-restriction analysis of EBV-specific T cells generated from the HSCT donor (mother; blue bars) or from the third-party donor 1 (brown bars) or third-party donor 2 (yellow bars) tested in a Cr51-release assay against a panel of allogeneic EBV-BLCLs, each matching 1 HLA allele of each of the T-cell donors' HLA types. (C) Monitoring of the EBV DNA levels (red line) and EBV-specific T cells (green line) after infusions of EBV-CTLs derived from the stem cell donor (blue arrows), third-party donor 1 (purple arrow), and third-party donor 2 (red arrows) at the doses of 1 × 106 cells/kg/infusion. Treatment with Rituxan (375mg/m2; orange arrows), as well as injections of EBV-CTLs derived from the HSCT donor that were restricted by the donor-unique HLA A1101 allele, did not affect high levels EBV DNA, whereas the administration of the EBV-specific T cells from the third-party donors 1 and 2, both restricted by the A2601 HLA allele presented on the EBV+ tumor cells of patient origin, resulted in a rapid decrease of the EBV DNA in the circulation. (D) Sequential PET scans demonstrating no response to the transplant donor's T cells with rapid development of an EBV lymphoma of the gastric wall and adjacent lymph nodes. By 3 weeks after the first infusion of third-party T cells (d97), gastric lymphoma was no longer detected.

Basis for nonresponse: donor-derived EBV-specific T cells did not recognize host origin EBV-LPD (patient 8). (A) HLA type of the stem cell donor (mother), third-party EBV-CTLs donor 1, and third-party EBV-CTL donor 2. (B) HLA-restriction analysis of EBV-specific T cells generated from the HSCT donor (mother; blue bars) or from the third-party donor 1 (brown bars) or third-party donor 2 (yellow bars) tested in a Cr51-release assay against a panel of allogeneic EBV-BLCLs, each matching 1 HLA allele of each of the T-cell donors' HLA types. (C) Monitoring of the EBV DNA levels (red line) and EBV-specific T cells (green line) after infusions of EBV-CTLs derived from the stem cell donor (blue arrows), third-party donor 1 (purple arrow), and third-party donor 2 (red arrows) at the doses of 1 × 106 cells/kg/infusion. Treatment with Rituxan (375mg/m2; orange arrows), as well as injections of EBV-CTLs derived from the HSCT donor that were restricted by the donor-unique HLA A1101 allele, did not affect high levels EBV DNA, whereas the administration of the EBV-specific T cells from the third-party donors 1 and 2, both restricted by the A2601 HLA allele presented on the EBV+ tumor cells of patient origin, resulted in a rapid decrease of the EBV DNA in the circulation. (D) Sequential PET scans demonstrating no response to the transplant donor's T cells with rapid development of an EBV lymphoma of the gastric wall and adjacent lymph nodes. By 3 weeks after the first infusion of third-party T cells (d97), gastric lymphoma was no longer detected.

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