john paquet iii bme 181 s01 08 april 2013. 2008 – 7.6 million deaths worldwide by cancer 13% of...
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John Paquet IIIBME 181 S0108 April 2013
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2008 – 7.6 million deaths worldwide by cancer
13% of total worldwide deaths that year
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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
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Blocking monoclonal anti-humanCD47 antibodies
Anti-hCD47 mAbs- include B6H12.2 and Bric126
Anti-hCD47 mAbs block CD47’s “don’t eat me” signal
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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
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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
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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
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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
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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
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"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>