No abstract

Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D repl; n=28) or T-cell-depleted (D depl; n=16) graft from a CMV-seropositive donor were screened for CMV-specific T-cell immunity. Eight D depl recipients received adoptive T-cell therapy from their stem cell donor. CMV epitope-specific T cells were well supported and became detectable in all treated patients. Complete and partial virological response rates were 62.5% and 25%, respectively. Owing to longsome third-party donor (TPD) identification, only 8 of the 57 CMV patients transplanted from CMV-seronegative donors (D) received antigen-specific T cells from partially human leukocyte antigen (HLA)-matched TPDs. In all but one, TPD-derived CMV-specific T cells remained undetectable. In summary, adoptive transfer correlated with functional virus-specific T-cell reconstitution in D depl patients. Suboptimal HLA match may counteract expansion of TPD-derived virus-specific T cells in D patients.

No abstract

A fusion protein containing a B cell lymphoma idiotype (Id) variable genes from the tumor and the preparation of and granulocyte-macrophage colony-stimulating factor tumor-specific vector constructs. The low production of (GM-CSF) is a potent stimulator of tumor immunity. In three Id/GM-CSF fusion proteins by transfected cells, which is different tumor models we show that immunization with a major obstacle in the use of purified fusion proteins for autologous lymphoma cells that have been engineered to immunotherapy, is due to the presence of the cytokine express the Id in the context of GM-CSF is much more gene in the immunoglobulin locus. Low production, howeffective than immunization with an equivalent dose of the ever, is not limiting in the cell-based setting, because upon purified protein. The lymphoma Id could be modified by in vivo administration of the modified autologous cells, introducing the GM-CSF gene into the immunoglobulin (Ig) even minute expression levels are sufficient to induce heavy chain locus via gene targeting. This approach cirtumor immunity. cumvents the isolation of the rearranged immunoglobulin