Research
We investigate basic immunological mechanisms to understand and ultimately strengthen graft-versus-leukemia (GvL) effects of donor immune cells after allogeneic hematopoietic stem cell transplantation in order to avoid leukemia relapse. We also study graft-versus-host immune reactivity to non-hematopoietic patient tissues (f.e. gut, skin), which we intend to prevent or at least mitigate by innovative immunomodulatory strategies.
CRC TRR 221's mission
Within the Collaborative Research Centre/Transregio (CRC/TRR) 221 innovative immune modulation strategies are investigated to separate graft-versus-host disease (GvHD) from GvL (graft-versus-leukemia) effects in order to enhance the safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) in the future.
Our Vision
Scientists of project area A analyze new molecular targets and cellular pathways (e.g. T cell receptor & chimeric antigen receptor transfer, multifunctional antibodies, minor histocompatibility antigen-specific T cells) to augment graft-versus-leukemia (GvL) responses and assess them in in vivo models (wherever reasonable). In project area B, scientists examine basic pathomechanisms of graft-versus-host-reactivity and develop new strategies for the prevention and/or therapy of this transplant complication. Here, the specific modulation of T cell signal transduction pathways is explored, regulatory molecular and cellular networks within innate and adaptive immune compartments are examined as well as GvHD-promoting co-factors, such as inflammatory pathways and microbiome alterations. Strategies aimed to strengthen GvL effects are always tested for their influence on GvHD and vice versa. The most promising strategies evolving from these studies shall be tested in future clinical trials to ultimately improve the safety and efficacy of allo-HSCT significantly.
What is GVH
GvL-promoting strategies carry the inherent risk of inducing graft-versus-host (GvH) disease, where donor T cells attack and damage non-hematopoietic tissues. The efficient prevention and treatment of severe GvHD is a pivotal prerequisite to benefit from allo-HSCT and its potent GvL effects. Hence, the elucidation of basic mechanisms in tissue-directed graft-versus-host responses is essential to reduce the high treatment-related morbidity and mortality in allo-HSCT. GvHD-free allo-HSCT is then an ideal immunotherapy platform to boost GvL responses for the cure of patients, including those with residual disease or relapse after transplantation.
What is GVL
The graft-versus-hematopoiesis reaction is mainly mediated by alloreactive donor T cells and affects also malignant hematopoietic cells, thereby evoking potent graft-versus-leukemia / lymphoma (GvL) effects. Although allo-HSCT offers a unique chance to rescue patients with otherwise incurable hematologic malignancies, still around one quarter of allo-HSCT recipients develop disease relapse or progression after transplantation. Thus, there is an urgent need to better understand and ultimately strengthen GvL responses to prevent tumor escape.
