Transcript Deep Brain Stimulation to Treat Alzheimer`s Disease

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>