WP03 - Clinical trial for the treatment of infections and tumor relapse after allogeneic HSCT

Objectives of the workpackage

The objective in work package 3 is to determine the safety and efficacy of adoptively transferring tumor-reactive and/or pathogen-specific T cells to patients after bone marrow transplantation in order to enhance anti-tumor efficacy, and reduce the risk of tumor relapse and infection in a clinical Trial

Workpackage description

T cells play a major role after bone marrow transplantation - they are key mediators of the potent and potentially curative Graft-versus-Leukemia (GvL) effect that leads to leukemia-control and eradication in a substantial fraction of patients, and they are critical for protecting the patient from infectious pathogens such as viruses.

There is evidence that leukemia-specific T cells can be generated from the bone marrow donor, expanded and infused to the patient after allogeneic HSCT in order to enhance the GvL effect, or confer an anti-leukemia effect in patients that failed to develop GvL reactivity; and that virus-specific T cells can be derived from the bone marrow donor in order to (re-)establish or enhance immunity to viral pathogens. However, strategies for the generation of such leukemia-/virus-specific T cells involve extensive and laborious ex vivo cell culture protocols that are difficult to adapt to large-scale clinical use.

In this work package, the investigators will address, whether leukemia-reactive and virus-specific T cells can be isolated from the peripheral blood of bone marrow donor with novel, highly sensitive cell selection strategies and be transferred directly after minimal manipulation to patients who have undergone bone marrow transplantation. The focus will be on determining, whether the transferred T cells confer an anti-leukemia/anti-virus effect in vivo.

The investigators will develop and compile all necessary documentation for the clinical trial, seek regulatory and ethics approval, and once approval has been obtained, treat and monitor eligible patients in a non-randomized, phase II clinical trial of using multi antigen-specific T cells to prevent leukemia relapse and infections after allogeneic HSCT.