Immune Tolerance of CLL Antigens

University Of California, San Diego, La Jolla CA

Investigators

Linked publications & trials

Abstract

The central hypothesis of this project is that the interaction of tumor cells with the host immune system[unreadable] results in specific T cell defects in the cancer bearing patients. Although the nature of these T cells defects[unreadable] is poorly understood, repair of these defects will be required to mount effective immune responses required[unreadable] for successful tumor vaccination. In studies modeled in chronic lymphocytic leukemia (CLL) we have[unreadable] documented functional defects in the ability of the T cells to mount anti-tumor responses. Global gene[unreadable] expression profiles of purified CD4 and CDS cells from CLL patients compared to CD4 and CDS cells from[unreadable] age matched healthy donors documented multiple defects. We now seek to characterize the basis for[unreadable] defective T cell function in CLL and repair these defects for future therapeutic intervention. We shall examine[unreadable] this in human samples from patients with CLL and in vivo in the Eu-TCL1 transgenic mouse model of CLL.[unreadable] We shall seek to identify the targets of T cell mediated resposnes against CLL cells and in particualr seek to[unreadable] characterize the nature of the graft versus leukemia effect in CLL. To address these issues we propose the[unreadable] following three specific aims. First, we shall characterize the defects in the CD4 and CDS cells of patients[unreadable] with CLL and in the Eu-TCL1 transgenic mouse model of CLL. Second we shall seek to identify the targets of[unreadable] T cell mediated responses against CLL cells and maximize these responses in vitro and in vivo. Third, we[unreadable] shall identify whether allogeneic T cell responses against CLL cells are targeted against CLL antigens or[unreadable] against minor histocompatibility antigens.[unreadable] Patients fail to mount an immune response against their cancers and cancer cells impair patients' immunity.[unreadable] Using chronic lymphocytic leukemia as a model, we aim to identify how cancer cells impair immune function,[unreadable] repair these immune defects and assess how we can increase immune responses against cancer cells.[unreadable] These findings are likely to lead to improvements in outcome after allogeneic stem cell transplants and to[unreadable] help us to develop cancer vaccines inthis and other cancers.