![]() ![]() The registry compiles screening results on the specific memory T-cell repertoire of potential donors in response to CMV, EBV, and ADV and is now extended to polyoma virus (BK) and HHV6 and thus will accelerate the adoptive T-cell therapy. One promising option for providing potential T-cell donor is the allogeneic cell registry ( alloCELL, ), which was established at Hannover Medical School within the last three years. The efficient treatment of high risk patients with seronegative donors requires the rapid recruitment of a suitable seropositive T-cell donor as well as an established and robust protocol for the timely manufacturing of antiviral T cells without long-term ex vivo stimulation. Recent studies have shown that the adoptive transfer of T cells with selected antigen-specificities is an effective and safe treatment option for enhancing the long-term protection of patient immunity after engraftment and immune reconstitution without increasing the risk of GvHD -,. Treatment with donor lymphocyte infusions (DLI) routinely separated from the seropositive stem cell donor can improve the clinical outcome of viral infection and leukaemia relapse, but it is (i) associated with a high risk of inducing graft-versus-host disease (GvHD), (ii) attended with impaired functionality of antiviral memory T cells in granulocyte colony-stimulating factor- (G-CSF-) mobilized stem cell donors -, (iii) not suitable in high risk patients with seronegative donors and (iv) not available for patients receiving cord blood in HSCT or cadaveric transplants in SOT. Functionally active antiviral T cells are crucial for the effective elimination and control of those life-threatening viral infections or reactivations. The lack or low frequency of antiviral T cells and the delay in virus-specific T-cell reconstitution are critical factors in virally infected post-transplant patients. Infection or reactivation with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), and human herpesvirus (HHV) 6 are the most common causes of viral morbidity and mortality after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). The generation of antiviral CD4 + and CD8 + T cells by CliniMACS CCS can be extended to a broad spectrum of common pathogen-derived peptide pools in single or multiple applications to facilitate and enhance the efficacy of adoptive T-cell immunotherapy. The enriched T-cell products were stable over 72 h with respect to viability and ratio of T lymphocytes. In addition to T cells and NKT cells, all preparations contained acceptably low percentages of contaminating B cells, granulocytes, monocytes, and NK cells. Using the CMVpp65 peptide pool for restimulation resulted in the activation of more CMV-specific CD8 + than CD4 + memory T cells, both of which were effectively enriched to a total of 81.0% CD8 +IFN-γ + and 38.4% CD4 +IFN-γ + T cells. Potential T-cell donors were selected from alloCELL and defined as eligible for clinical-grade antiviral T-cell generation if the peripheral fraction of IFN-γ + T cells exceeded 0.03% of CD3 + lymphocytes as determined by IFN-γ cytokine secretion assay. ![]() TEXMACS GMP MEDIUM LICENSETo obtain a manufacturing license according to the German Medicinal Products Act, the enrichment of clinical-grade CMV-specific T cells from three healthy CMV-seropositive donors was performed aseptically under GMP conditions using the CliniMACS cytokine capture system (CCS) after restimulation with an overlapping peptide pool of the immunodominant CMVpp65 antigen. Therefore we established a registry of potential third-party T-cell donors (allogeneic cell registry, alloCELL) providing detailed data on the assessment of a specific individual memory T-cell repertoire in response to antigens of cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), and human herpesvirus (HHV) 6. Allogeneic third party T-cell donors offer an alternative option for patients receiving an allogeneic cord blood transplant or a transplant from a virus-seronegative donor and since donor blood is generally not available for solid organ recipients. ![]() The adoptive transfer of allogeneic antiviral T lymphocytes derived from seropositive donors can safely and effectively reduce or prevent the clinical manifestation of viral infections or reactivations in immunocompromised recipients after hematopoietic stem cell (HSCT) or solid organ transplantation (SOT). ![]()
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