Weissman and Jens Volkmer, MD, postdoctoral research fellow, in urology, Matt van de Rijn, MD, PhD, professor of pathology, Kelli Montgomery, research assistant, and Badreddin Edris, MS, graduate student, are collaborating with Harvard Medical School’s George Demetri, MD, associate professor of medicine, and Jonathan Fletcher, MD, associate professor of pathology, to investigate the effects of blocking anti-CD47 antibodies on human leiomyosarcomas (LMS) and gastrointestinal stromal tumors (GIST).
- They have found that macrophage infiltration and CFS1 expression in LMS are associated with poor outcome. In GIST there is no such effect on outcome, but sporadic GIST do contain high numbers of macrophages.
- They have observed a correlation between CD47 and CSF1 messenger RNA expression in a number of LMS cases, suggesting that LMS cells may be protected from phagocytosis by CD47. Preliminary experiments suggest that inhibition of CD47 on LMS cells leads to increased phagocytosis by macrophages. Experiments using xenografts made with LMS and GIST cell lines are ongoing.
- The currently existing monoclonal antibodies against CD47 react only with frozen tissue, which limits their application. Given the biological relevance of the CD47 molecule, a new CD47-reactive monoclonal antibody will be generated that will react in formalin-fixed, paraffin-embedded tissue. Such a reagent will make it possible to study hundreds of clinical tumor specimens with known follow-up.