In-Labeled recombinant gelonin toxin-B lymphocyte stimulator protein fusion protein

The B lymphocyte stimulator (BLyS; for other synonyms see Summary Table above) is a glycoprotein belonging to the tumor necrosis factor cytokine family and promotes the survival, proliferation, and differentiation of the B cells (2). Three different receptors on the B cells (for details, see Wen et al. (2)) are known to bind BLyS; among these, the B cell–activating factor receptor shows the strongest affinity for this cytokine. Although BLyS is overexpressed on B cells of individuals suffering from autoimmune diseases such as lupus, rheumatoid arthritis, etc., the BLyS receptors are known to be expressed on the membrane surface of several types of cancerous tumor cells [PubMed]. Because of its specificity of binding to B cells, BLyS-derived fusion toxins such as the gelonin (Gel)-BLyS fusion protein has been studied by investigators to selectively target and treat B cell malignancies (3-6). Gel is an -glycosidase type I ribosome-inactivating plant toxin that lacks a cell binding or a cell internalization domain and is almost non-toxic to intact cells (2, 7). However, mammalian cells can internalize the toxin in association with a carrier, at which point Gel is lethal to the cells because it inhibits protein synthesis completely within 3–4 days of internalization and release within the cell. Recently a recombinant Gel (rGel)-BLyS fusion protein (rGel/BLyS) was constructed by linking rGel to the -terminus of BLyS, and rGel/BLys was labeled with In using diethylenetriamine pentaacetic acid (DTPA) to produce the radionuclide chelator [In]-DTPA-rGel/BLyS (2). The biodistribution and tumor-imaging characteristics of [In]-DTPA-rGel/BLyS were then studied in severe combined immunodeficient (SCID) mice bearing B cell lymphoma tumors (2).