Leukotrienes (LTs) and lipoxins (LXs) are local mediators formed rapidly within the microenvironment of vascular lumen and at sites of inflammation during cell-cell interactions.1 In these inflammatory circuits LX counter not only LT bioactions but also their formation.2 Inflammatory diseases are associated with an increase in specific mediators, their receptors, as well as key pathways such as cyclooxygenase II and lipoxygenase. [2][3][4][5] In humans, an array of symptoms are often treated with aspirin (ASA), a lead nonsteroidal anti-inflammatory drug that has beneficial actions that can surpass ASA's well-appreciated ability to inhibit prostaglandin generation in certain clinical settings. These include prevention of cardiovascular diseases as well as decreasing the incidence of lung, colon, and breast cancer.6 Unlike other nonsteroidal antiinflammatory drugs that inhibit cyclooxygenase II, ASA also switches the enzyme's activity from prostaglandin endoperoxide synthesis to an R-lipoxygenase that initiates the biosynthesis of endogenous analogues of LX, namely 15-epimeric-LX, also termed aspirin-triggered LX (ATL, 5S,6R,15R-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid). These enantiomers of native LX display enhanced anti-leukocyte actions that accompany the chiral switch from S to R at carbon 15 in aspirin-triggered LXA 4 .2

We isolated a tumor B-cell-targeting antibody, BI-505, from a highly diversified human phage-antibody library, using a pioneering "function-first" approach involving screening for (1) specificity for a tumor B cell surface receptor, (2) induction of tumor programmed cell death, and (3) enhanced in vivo antitumor activity compared to currently used treatments. BI-505 bound to intercellular adhesion molecule-1, identifying a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope was strongly expressed on the surface of multiple myeloma cells from both newly diagnosed and relapsed patients. BI-505 had potent macrophage-dependent antimyeloma activity and conferred enhanced survival compared to currently used treatments in advanced experimental models of multiple myeloma.

No abstract