BLys inhibition using TACI-Fc in patients with B-bell non-Hodgkins' Lymphoma

Project: Research project

Project Details


B-cell malignancies are the sixth most common cause of cancer-related deaths in the United States. While some
aggressive lymphomas may be cured with cytotoxic therapy, most patients are incurable with current therapy. Novel
effective therapies are therefore needed to treat these patients.
B-lymphocyte stimulator (BLyS) is a TNF-family molecule that promotes B-cell survival and is a key regulator of
peripheral B-cell populations. It binds to three receptors - BCMA, TACI and BAFF-R. We have shown that malignant B-
cells can produce BLyS and that cells from patients with B-cell malignancies commonly express TACI and BAFF-R. We
have found that BLyS protects malignant B-cells from apoptosis and that serum BLyS levels in lymphoma patients
correlate with response to therapy and overall survival. We have also found that patients with a family history of B-cell
malignancies have a higher incidence of elevated serum BLyS levels and this is associated with a polymorphism in the
BLyS promoter region. It is therefore anticipated that molecules that inhibit the effects of BLyS will provide a novel
strategy to treat patients with B-cell malignancies.
TACI-Fc is a recombinant fusion protein containing the extracellular, BLyS-binding portion of the receptor TACI and the
modified Fc portion of human lgG1. TACI-Fc acts as an antagonist to BLyS by working as a decoy receptor that binds
BLyS thereby potentially decreasing the pro-survival signal in B-cell malignancies. In collaboration with ZymoGenetics
and Serono, we have designed a phase I clinical trial and a subsequent extension study to evaluate the optimal dose
and potential activity of TACI-Fc. In this proposal, we plan to determine the biological effects of BLyS inhibition on
malignant B-cells in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia and to evaluate whether
this will lead to an improved clinical outcome for patients with B-cell malignancies.
StatusNot started


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.