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Anti-hCD47 Antibody: Potential Cure for Cancer

Anti-hCD47 Antibody: Potential Cure for Cancer. John Paquet III BME 181 S01 08 April 2013. Cancer’s Toll. 2008 – 7.6 million deaths worldwide by cancer 13% of total worldwide deaths that year. Cellular Cloaking Device. CD47- protein that coats surface of cells

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Anti-hCD47 Antibody: Potential Cure for Cancer

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  1. Anti-hCD47 Antibody: Potential Cure for Cancer John Paquet III BME 181 S01 08 April 2013

  2. Cancer’s Toll • 2008 – 7.6 million deaths worldwide by cancer • 13% of total worldwide deaths that year

  3. Cellular Cloaking Device • 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

  4. The Antibody • Blocking monoclonal anti-humanCD47 antibodies • Anti-hCD47 mAbs- include B6H12.2 and Bric126 • Anti-hCD47 mAbs block CD47’s “don’t eat me” signal

  5. “Don’t Eat Me” to “Eat Me” • 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 calreticulinon surface, so macrophages don’t consume them

  6. Results on Mice • 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

  7. Results (Cont.) • 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

  8. Risks/Disadvantages • Large doses of anti-hCD47 mAbsproduce 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

  9. Discussion • 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

  10. References • "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-cd47-miracle-bullet-breast-colon-bladder-antibody-eat-macrophage-immune.htm>

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