The cellular facility, alloCELL was recently been established for the purpose of identifying suitable T cells donors, providing personalized antiviral T-cell immunotherapeutics to patients in need, and monitoring programs for pathogen-specific T cells in patients after transplantation.
alloCELL: Donor registry and personalized antiviral T-cell immunotherapeutics
Infectious complications caused by herpesviruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesvirus (HHV)-6 as well as by lytic viruses such as adenovirus (ADV) are the most common causes of viral morbidity and mortality after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). Antiviral agents can reduce the incidence of early viral diseases but are associated with substantial toxicity and may result in delayed immune reconstitution.
The adoptive transfer of allogeneic antiviral T lymphocytes derived from seropositive donors can safely and effectively reduce or prevent the clinical manifestation of these viruses in patients with no acute toxicities or increased risk of graft-versus-host disease (GvHD) following transplantation.
The isolation of clinical-grade antiviral T cells is restricted to antigens for which moderate or high T-cell frequencies are present in the peripheral blood of potential T cell donors. Unfortunately, for patients receiving an allogeneic cord blood (CB) transplant, a solid organ transplant or a transplant from a virus-seronegative donor no T-cell donor will be available. For this reason, a rapid recruitment of a respective T-cell donor and an established method for a fast manufacturing of antiviral T cells without long-term ex vivo culture are of great importance.
A registry of potential third-party T-cell donors (allogeneic cell registry, alloCELL) has been established in 2013 at Hannover Medical School. The registry document each donor's HLA type (class I and II), virus serology (ADV, CMV, EBV), virus-specific T-cell frequencies, best T-cell detection method, and results from functional and alloreactivity assays. The registry provide detailed data on the assessment of the specific individual memory T-cell repertoire in response to antigens of CMV, EBV, HHV6 and ADV and is now extended to polyoma virus (BK) as well as to melanoma (Melan-1/Mart-1) and tumor antigens (WT-1).
HLA-typed allogeneic T-cell donors are characterized for specific T cells first by ELISpot and then undergo a detailed phenotypic and functional analysis using pMHC multimer staining and cytokine secretion assays. More than 1350 blood and platelet donors are record in the registry with information about the memory T-cell repertoire for more than 550 donors. The growing number of donors will ensure the rapid availability of T cells for virus-associated diseases in transplant recipients without an adequate T cell donor.
The enrichment of clinical-grade antigen-specific T cells from donors is performed aseptically under GMP conditions using the IFN-γ CliniMACS cytokine capture system (CCS) and overlapping GMP-grade peptide pools spanning the entire sequence of an immunogenic epitope. The manufacturing license by the local authorities was granted by March 27th, 2014.
If you have a patient, who is in need of
- a third party T-cell donor from alloCELL registry and/or
- a personalized antiviral T-cell immunotherapeutics
- monitoring virus-specific T cells in pheripheral blood
please contact us.
If you will be recorded in the registry please contact us
The following T-cell products are manufactured in the GMP facility of Hannover Medical School:
alloCELL-Vir Antiviral T cells restricted against viral epitopes
EBV: select, EBNA-1
Multiple epitopes for CMV, EBV and ADV
HHV6: U54, U90 (under development)
alloCELL-Tum T cells restricted against WT-1
alloCELL-Mel T cells restricted against Mart-1/Melan-A/Mart-1
Prof. Dr. Britta Eiz-Vesper
Institute for Transfusion Medicine
Hannover Medical School