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John Paquet III BME 181 S01 08 April 2013 2008 – 7.6 million deaths worldwide by cancer 13% of total worldwide deaths that year CD47- protein that coats surface of cells “Don’t eat me” signal to immune cells Cancer cells boost their CD47 levels Macrophages ignore the cancer Blocking monoclonal anti-humanCD47 antibodies Anti-hCD47 mAbs- include B6H12.2 and Bric126 Anti-hCD47 mAbs block CD47’s “don’t eat me” signal SIRPα on macrophages binds to CD47 Resulting signaling cascade inhibits phagocytosis Anti-hCD47 mAb specifically binds to antigen CD47 to block “don’t eat me” signal Cancer cells also output “eat me” signal- calreticulin Disabling CD47 barrier exposes calreticulin “eat me” signal Normal cells do not have calreticulin on surface, so macrophages don’t consume them In one mouse, human leukemic cancer was completely gone 1 day after single dose of antibody injected In mice with human acute myelogenous leukemia, cancer was erased in a majority of the mice Large tumors shrink, some smaller ones even vanish Also successful at treating cancers that have already spread Anti-hCD47 mAbs prevent cancer from metastasizing Greater the amount of CD47 expressed by cancer cells, the lesser the chance that subject survived ◦ Dosage can be increased Effectiveness of antibody therapy was inversely proportional to initial tumor size Large doses of anti-hCD47 mAbs produce temporary amenia ◦ Red blood cell count recovers quickly Not advisable after chemotherapy ◦ Normal cells are damaged due to high stress, so they have calreticulin on surface- “eat me” signal ◦ Disabling CD47 would enable phagocytosis of normal cells Can be grown in unlimited amounts would likely be most effective when: ◦ tumor is maximally debulked ◦ used alongside antibodies that strengthen the “eat me” signals from surface proteins like calreticulin Potential to treat nearly every type of cancer $20 million grant from CIRM Human trials to begin late 2013 or early 2014 "Cancer." World Health Organization, Jan. 2013. Web. <http://www.who.int/mediacentre/factsheets/fs297/en/> "Monoclonal Antibodies." Wikipedia. Wikimedia Foundation, 29 Mar. 2013. Web. <http://en.wikipedia.org/wiki/Monoclonal_antibodies> "The CD47-signal Regulatory Protein Alpha (SIRPa) Interaction Is a Therapeutic Target for Human Solid Tumors." PubMed Central. National Academy of Sciences, 26 Mar. 2012. Web. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340046/> Vaughan, Christopher. "Cancer Roundhouse: Evidence Mounts That a Single Antibody Could Knock out Many Cancers." Stanford Medicine, Summer 2012. Web. <http://stanmed.stanford.edu/2012summer/article7.html> Weiss, Jonathan. "Scientists Have Silver Bullet To Kill Multiple Cancers, Human Trials Starting." Medical Daily, 28 Mar. 2013. Web. <http://www.medicaldaily.com/articles/14434/20130328/cancer-treatment-cd47miracle-bullet-breast-colon-bladder-antibody-eat-macrophage-immune.htm>