Health Monoclonal_antibodies4

Published on March 27th, 2012 | by Michael Ricciardi

7

Cancer Treatment Breakthrough: A Single Antibody Drug Found to Shrink or Halt 'All Tumors'

Buffer this pageShare on Google+Share on RedditShare on FacebookTweet about this on TwitterPin on PinterestShare on StumbleUponShare on TumblrShare on LinkedInDigg thisEmail this to someone

March 27th, 2012 by

medical research (monoclonal antibodies)

 

[UPDATED: Sept. 2013; see update note at bottom] A biomedical research team at Stanford University School of Medicine reported yesterday the results of mouse  experiments using an antibody molecule to treat various types of tumorous cancer cells — with results showing significant tumor shrinkage and slowed tumor growth in all cancer cell types tested. In some cases, the tumorous cells were completely destroyed by host immune cells with no recurrences four months after the treatment was stopped.

This breakthrough results from the application of an earlier discovery by Irving Weissman some ten years ago showing that a certain cell marker protein — known as CD47 — normally found on the surfaces of blood cells, serves as a biological “flag” to immune cells, telling them “don’t eat me”. As it turns out, cancer cells have found away to exploit this innate host protection by secreting the same molecular flag as normal blood cells. Macrophages — large “killer cells” of the immune system — “see” the correct flag, and generally leave the cancer cells alone to replicate, and even metastasize (i.e., spread throughout the body).

In just the past few years,  the research team, led by Dr. Weissman, developed an antibody that blocks production of the CD47 cell marker, and then more recently began trying out the antibody on blood cancers such as leukemia.

“What we’ve shown is that CD47 isn’t just important on leukemias and lymphomas. It’s on every single human primary tumor that we tested.”, said Weissman [source: Science Now].

The team also discovered that tumor cells tended to produce higher levels of CD47 on their surface membranes than did healthy cells. Thus, the amount of CD 47 produced by a given type of cancer cell could be used as a predictor of patient recovery.

Anti-CD47 antibodies enable macrophage phagocytosis of tumor cells.

Anti-CD47 antibodies enable macrophage (red) phagocytosis of tumor cells  (larger green spots).

In theory, blocking the production of this molecular flag on the surface of tumor cells should then make them detectable to the body’s protective immune cells.

To test this hypothesis, in vitro experiments were conducted first using tumor cells grown in petri dishes and exposing them to macrophages, with and without the additional antibody. Without the anti-CD47 drug, the macrophages did not recognize the cancer cells as alien, and left them alone. But when the antibody was present in the culture, the macrophages quickly engulfed and eventually destroyed the tumor cells. This anti-cancer activity, known as phagocytosis, was demonstrated with every type of tumor.

The team next tested out the drug on mice who were given transplants of various human tumors. When the mice were then treated with the anti-CD47 drug, the tumors decreased in size and failed to metastasize. The process was repeated with other human tumor transplants such as colon cancer tumors. The team found that these tumors shrank to less than one third of their original size on average. And in mice with breast cancer tumors, the drug eradicated all sign of the tumors, with the mice remaining cancer free for four months after cessation of the treatment.

anti-CD47 antibodies

Advanced phagocytosis of cancer cells by Macrophages after anti-CD47 antibody treatment

Although this treatment also rendered blood cells susceptible to immune cell targeting, this ill effect was transient and red blood cells levels eventually recovered to normal levels.

“We showed that even after the tumor has taken hold, the antibody can either cure the tumor or slow its growth and prevent metastasis.” said Weissman [source: Science Now].

While quite promising, other researchers say that the transplanted tumors do not possess the same ‘micro environments’ as ‘real’ tumors (which have additional immune suppressing tricks) and question if the same results will be achieved in humans. Others also wonder about how this antibody will interact with other medications; an antagonistic effect could result, possibly causing cells stressed from chemotherapy to over-produce CD47.

That said, the results from these recent experiments are undeniably positive and compelling enough to justify moving ahead with more advanced testing: from mice to humans.

The Stanford team has already received a  $20 million grant from the California Institute for Regenerative Medicine to initiate planning of human safety trials.

The results of these experiments were published yesterday (March 26, 2012, submitted in Dec. 2011) in the  Proceedings of the National Academy of Sciences, under the title:  The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors (Willingham et al, 2012)

Quote (from the paper’s Abstract):

“These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.”

UPDATE (Sept. 2013): Additional testing of the experimental antibody treatment has been conducted with promising results, showing that “anti-CD47 antibody–mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response.” The researchers (Tseng et al) also found that macrophages recruited to tumor sites not only phagocytosed the cancer cells but “primed CD8+ T cells to exhibit cytotoxic function in vivo. This response protected animals from tumor challenge.” The abstract and full paper can be found on the PNAS website.

Top Image:  National Cancer Institute

Additional Photos: (phagocyctosis) Supporting Information, PNAS

Keep up to date with all the most interesting green news on the planet by subscribing to our (free) Planetsave newsletter.




Buffer this pageShare on Google+Share on RedditShare on FacebookTweet about this on TwitterPin on PinterestShare on StumbleUponShare on TumblrShare on LinkedInDigg thisEmail this to someone

Tags: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,


About the Author

Michael Ricciardi is a well-published writer of science/nature/technology articles as well as essays, poetry and short fiction. Michael has interviewed dozen of scientists from many scientific fields, including Brain Greene, Paul Steinhardt, Arthur Shapiro, and Nobel Laureate Ilya Progogine (deceased). Michael was trained as a naturalist and taught ecology and natural science on Cape Cod, Mass. from 1986-1991. His first arts grant was for production of the environmental (video) documentary 'The Jones River - A Natural History', 1987-88 (Kingston, Mass.). Michael is an award winning, internationally screened video artist. Two of his more recent short videos; 'A Time of Water Bountiful' and 'My Name is HAM' (an "imagined memoir" about the first chimp in space), and several other short videos, can be viewed on his website (http://www.chaosmosis.net). He is also the author of the (Kindle) ebook: Artful Survival ~ Creative Options for Chaotic Times



  • medical

    Hello everyone,
    High Quality cancer hemp oil on Sale at negotiable prices
    Cancer hemp oil on sale at excellent rate
    Medicinal value
    Contact: +447924590270
    Email: cancermedicationtreatment@gmail.com
    Delivery as Per Customer Requirements.

  • medical

    Hello everyone,
    High Quality cancer hemp oil on Sale at negotiable prices
    Cancer hemp oil on sale at excellent rate
    Medicinal value
    Contact: +447924590270
    Email: cancermedicationtreatment@gmail.com
    Delivery as Per Customer Requirements.

  • Eugene Jambor

    Wife has leyomeyo sarcoma under right Kidney. Started in the Uterous which has been removed with same type tumor in it. Two years of targeted insulin potentiation therapy have not slowed growth but have reduced FDG uptake ( pet scan) No idea where to go from here. Please help..

  • Nick AbouMossa

    And then the pharmaceutical companies……SAY THEE NAY!

  • Bobv Morgan

    Many others will think or say: “if only…”. We lost a son, age 46, only 5 years ago. Please contimue and accelerate this resarch if possible. How can we help?

  • http://plantsave.com David G. Diaz

    Are there any trials going on with this study? If there is where can we sign someone up? My mother has been dealing with overian cancer for the last 2-1/2-3 years and it has becoming more agressive. We are running out of time soon. We are willing to try anything at this point. Sound like from the testing it works well. If you don’t know of trials, could you please direct me in the direction of the person or people. I could get into contact to: I would appricate any help you can give. We are in San Marcos, Tx between Austin, Tx and San Antonio, Tx. My mother as of right now is in Seton Main in Austin, Tx. Please help me if you can!

    Thank you,

    David G. Diaz

    • http://www.chaosmosis.net Michael Ricciardi

      Thanks for your comment.

      Human trials are expected to start sometime this summer, but there are often delays.

      I don’t know about signing up for this study as it will be some type of double blind/placebo/control study (most likely) and study subjects would be assigned randomly.

      You can try a search on the institutions listed in the article and see if you can find a contact.

Back to Top ↑