GRAFT VERSUS TUMOR

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

Allogeneic BMT was first considered as a method of providing tumor- free marrow. It has been shown in the laboratory and clinic that there are immunologic anti-tumor effects of allogeneic BMT. This effect has been linked to the occurrence of Graft versus Host disease (GVHD). The ability to exploit this Graft versus-Leukemia (GVL) effect has been difficult. The goal of this project is to expand our understanding of this allogeneic anti-tumor effect by studying it in the laboratory in animal models and from patient samples obtained from the proposed clinical trials. We will try to augment the GVL effects of Donor Leukocyte Infusions (DLI) by subverting the mechanisms underlying the establishment of graft-host tolerance following allogeneic BMT. Although we will examine immunologic responses in animal models of DLA and GVHD (acute, chronic, and autologous) for GVL, our major emphasis will be on the balance between T cell activation and tolerance in controlling allogeneic responses. We will explore the role of antigen presenting cells which we postulate play a pivotal role (by their presence or absence) in regulating GVL. Immunologic responses of patients in a DLI trials will be characterized using functional and flow cytometric techniques. Finally, we will determine the optimal IL-2 dose to augment the GVL effect seen after lymphocyte depleted marrow grafts in a clinical and laboratory trial. IL-2 will be dose escalated based on effects on NK and T cell function measured in the laboratory instead of a traditional maximum tolerated dose escalation study. At the end of this project we should have an improved understanding of GVL and of methods to try to maximize the GVL effect.