John Paquet III BME 181 S01 08 April 2013. 2008 – 7.6 million deaths worldwide by cancer 13% of...
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Transcript of John Paquet III BME 181 S01 08 April 2013. 2008 – 7.6 million deaths worldwide by cancer 13% of...
John Paquet IIIBME 181 S0108 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-cd47-miracle-bullet-breast-colon-bladder-antibody-eat-macrophage-immune.htm>