Anti-tumor activity of an ICAM-3 antibody (ICM3) Against human leukemic xenograft tumors in nude mice

Abstract

Intercellular Adhesion Molecule (ICAM)-3 is a hematopoietic specific counter receptor for a subset of beta 2 integrins. Previously, we observed that specific murine monoclonal antibody (mAb) engagement of ICAM-3 led to apoptosis of a bone marrow-derived myeloid cell population and leukemic cell lines Jurkat and U937 in vitro. Here, we test a proapoptotic anti-ICAM-3 mAb for inhibition of leukemic cell tumor growth in vivo using a nude mouse xenograft model. Initially, the humanized mAb, ICM3, was evaluated for the capacity to trigger apoptosis of Jurkat cells in vitro and was found to do so (P=.034 as compared to control antibody-treated cells). Next, nude mice with solid tumors derived from U937 cells received either ICM3 (n=45) or placebo (n=43) on day 0, 3 and 5. Tumor size was monitored over a 7-day period after which animals were sacrificed and tumors weighed, measured and examined by histology. ICM3 treatment resulted in significantly smaller U937 tumor volumes on days 4, 5, and 6 relative to placebo treatment (p=.016, .012, and .012, respectively). Median volume (interquartile range) of tumors excised on day 7 was 283 (151–451) mm3 for the placebo-treated group versus 137 (60–385) mm3 for the ICM3-treated group (p=.010). Histologic analysis revealed evidence of co-localization of ICM3 with antigen-bearing cells at the site of tumor formation. Taken together, these data document that treatment of leukemic tumors with ICM3 results in reduced tumor growth in vivo.