About the TRACE Project

Allogeneic stem cell transplantation is a curative treatment for a variety of diseases. However, refractory viral infections, such as Cytomegalovirus (CMV), Adenovirus (AdV) and Epstein-Barr virus (EBV) after stem cell transplantation are life-threatening conditions due to the deficient T-cell response and lack of effective treatment options.

Although cellular immunotherapy is considered a major breakthrough in medicine, none of the cellular treatment approaches has yet become a standard treatment. The reason for this limited translation into daily clinical practice is the lack of controlled, prospective clinical trials investigating efficacy of immunotherapy.

TRACE ("TRansfer of Adenovirus, Cytomegalovirus and Epstein-Barr virus-specific T cells") is the first multi-national clinical phase-III trial to prove efficacy and safety of Adoptive T-cell transfer in immunocompromised individuals. TRACE will provide data, approvals of national authorities and logistics to overcome regulatory and structural hurdles.

The study is a major milestone in the development of medicine and health economics to bring such a unique personalised treatment approach into a clinical efficacy trial. Further, it will bring medicine towards physiological self-protection of the human body instead of toxic, cost-intensive agents and will thereby improve survival and quality of life of the patients.

Virus-specific T cells becoming a Therapeutic Product

Different strategies have been developed to enrich, isolate or purify virus-specific T cells. For the TRACE study, the Cytokine Capture Technique was chosen due to the advantages of isolation of cytotoxic as well as T-helper cells, isolation of functional T-cell clones and of clones against known as well as unknown viral epitopes. Further this approach is available for patients and donors of all HLA-types.

In the TRACE study multivirus-specific (CMV, AdV and EBV-specific) T cells are isolated from blood of seropositive donors by an instrument called CliniMACS® Prodigy. The CliniMACS® Prodigy allows automated manufacturing of this T-cell product for adoptive T-cell therapy via the Cytokine Capture Technique and performs all steps in a functionally closed system.

Within T-cell product manufacture, the cellular starting material is incubated with specific Cytomegalovirus (CMV), Adenovirus (AdV) and Epstein-Barr virus (EBV) antigens. As a consequence, only the virus-specific T cells are induced to produce cytokines as they do under physiological conditions upon viral infection. These virus-specific, cytokine-secreting cells are labelled and conjugated to magnetic particles for the following enrichment using a magnetic column.