04-08-2013, 06:10 AM
Few statements in medical science are met with as much skepticism as the words, “We found a cure for cancer.” Cancer is a description given to more than 100 distinct diseases, affecting almost every part of the body. Cancer is caused when normal cells accumulate various mutations, or changes to the DNA that remove normal barriers to cellular replication. Thus, the mutated cancerous cell can replicate more frequently than normal cells, causing a tumor. If enough mutations accumulate, the cancerous cells can begin to leave the original site, and spread, or metastasize, to other parts of the body. Different types of cancers result from different combinations of mutations to factors that regulate cell growth and replication. To find one cure for all cancers seems like an impossible goal, given the various causes, locations, and types of cancers.
One great hope for cancer treatments comes from the host immune system. Normally, when either a foreign cell or a defective host cell is present in the body, the immune system will attempt to kill the cell. This prevents disease, such as infection or cancer. However, many cancer cells are able to evade the host’s immune system, by producing and displaying proteins that tell the host they are normal.
One such protein that is found on normal human cells is CD47. In normal cells, CD47 is expressed at a low level that is still sufficient to protect them from the immune system. Cancer cells, on the other hand, express very high levels of CD47. In 2012, researchers found that anti-CD47 antibody was able to target human-origin tumor cells in mice. The antibody, which binds to CD47 and makes it ‘invisible’ to immune cells, allowed macrophages and other phagocytes to destroy the tumor cells. This prevented tumor growth, and in some cases even decreased the size of the tumors. Shrinking tumors and preventing growth can help prevent the spread of cancer to other parts of the body.
The anti-CD47 antibody was effective at reducing the size and growth of a variety of human tumors, including breast cancer, bladder cancer, glioblastoma, lung cancer, and ovarian cancer. In many mice, the tumor was completely destroyed, and the mice remained cancer free several months after the study was completed. Additionally, the antibody did not show severe toxic reactions in the mice; only short-term anemia was noted. This is because cancer cells have a much higher number of CD47 molecules on their surface than normal cells, so they are targeted much more efficiently by the CD47 antibody. This lack of toxicity is a drastic change from conventional cancer therapies, such as chemotherapy and radiation, which work by targeting and killing all rapidly-multiplying cells.
Now, clinical trials are being prepared to test the efficacy of anti-CD47 antibody in human patients, and hopefully will begin in 2014. It is a difficult process to move from animal-based studies into clinical trials for many reasons. The antibody used in the clinical trials must be ‘humanized’ so that it interacts with the correct cells. In addition, the antibody must be produced in large quantities under very exacting conditions to ensure safety. The setup of the clinical trial must also be carefully planned, so that any data obtained can be properly interpreted. Investigators must determine how much antibody to give, which patients will be eligible, how to compare study results to placebo results, and more.
While this news is exciting, given the variety of cancers the anti-CD47 antibody was able to recognize, it must be met with cautious optimism. The natural tumors found in human patients may have key differences from the transplanted tumors in the mice. For example, these tumor cells may have other defense mechanisms in place to protect against the immune system. In addition, not all tumors may be good targets for the anti-CD47 immunotherapy. Solid tumors might be the best candidates for this immunotherapy, as the antibody could easily be injected directly into the tumor. However, if the tumor is too large, the antibody might not be able to reach and bind to all the cancer cells, necessitating multiple treatments. Blood cancers, such as lymphoma and leukemia, may not be suitable targets for the antibody. Because they do not consist of solid tumors, it might be difficult to localize the antibody to the cancerous cells. Also, since normal blood cells also express small amounts of CD47, intravenous injection of anti-CD47 antibody might cause more pronounced and long-lasting anemia that what was demonstrated in the mouse models. Despite these concerns, the promises of anti-CD47 immunotherapy could revolutionize future cancer treatments.
References:
http://www.pnas.org/content/109/17/6662.full.pdf+html
http://news.sciencemag.org/sciencenow/20...umors.html
http://www.webmd.com/cancer/default.htm
http://www.huffingtonpost.com/2013/03/28...72708.html
http://stemcell.stanford.edu/CD47/
http://clinicaltrials.gov/ct2/about-studies/learn
One great hope for cancer treatments comes from the host immune system. Normally, when either a foreign cell or a defective host cell is present in the body, the immune system will attempt to kill the cell. This prevents disease, such as infection or cancer. However, many cancer cells are able to evade the host’s immune system, by producing and displaying proteins that tell the host they are normal.
One such protein that is found on normal human cells is CD47. In normal cells, CD47 is expressed at a low level that is still sufficient to protect them from the immune system. Cancer cells, on the other hand, express very high levels of CD47. In 2012, researchers found that anti-CD47 antibody was able to target human-origin tumor cells in mice. The antibody, which binds to CD47 and makes it ‘invisible’ to immune cells, allowed macrophages and other phagocytes to destroy the tumor cells. This prevented tumor growth, and in some cases even decreased the size of the tumors. Shrinking tumors and preventing growth can help prevent the spread of cancer to other parts of the body.
The anti-CD47 antibody was effective at reducing the size and growth of a variety of human tumors, including breast cancer, bladder cancer, glioblastoma, lung cancer, and ovarian cancer. In many mice, the tumor was completely destroyed, and the mice remained cancer free several months after the study was completed. Additionally, the antibody did not show severe toxic reactions in the mice; only short-term anemia was noted. This is because cancer cells have a much higher number of CD47 molecules on their surface than normal cells, so they are targeted much more efficiently by the CD47 antibody. This lack of toxicity is a drastic change from conventional cancer therapies, such as chemotherapy and radiation, which work by targeting and killing all rapidly-multiplying cells.
Now, clinical trials are being prepared to test the efficacy of anti-CD47 antibody in human patients, and hopefully will begin in 2014. It is a difficult process to move from animal-based studies into clinical trials for many reasons. The antibody used in the clinical trials must be ‘humanized’ so that it interacts with the correct cells. In addition, the antibody must be produced in large quantities under very exacting conditions to ensure safety. The setup of the clinical trial must also be carefully planned, so that any data obtained can be properly interpreted. Investigators must determine how much antibody to give, which patients will be eligible, how to compare study results to placebo results, and more.
While this news is exciting, given the variety of cancers the anti-CD47 antibody was able to recognize, it must be met with cautious optimism. The natural tumors found in human patients may have key differences from the transplanted tumors in the mice. For example, these tumor cells may have other defense mechanisms in place to protect against the immune system. In addition, not all tumors may be good targets for the anti-CD47 immunotherapy. Solid tumors might be the best candidates for this immunotherapy, as the antibody could easily be injected directly into the tumor. However, if the tumor is too large, the antibody might not be able to reach and bind to all the cancer cells, necessitating multiple treatments. Blood cancers, such as lymphoma and leukemia, may not be suitable targets for the antibody. Because they do not consist of solid tumors, it might be difficult to localize the antibody to the cancerous cells. Also, since normal blood cells also express small amounts of CD47, intravenous injection of anti-CD47 antibody might cause more pronounced and long-lasting anemia that what was demonstrated in the mouse models. Despite these concerns, the promises of anti-CD47 immunotherapy could revolutionize future cancer treatments.
References:
http://www.pnas.org/content/109/17/6662.full.pdf+html
http://news.sciencemag.org/sciencenow/20...umors.html
http://www.webmd.com/cancer/default.htm
http://www.huffingtonpost.com/2013/03/28...72708.html
http://stemcell.stanford.edu/CD47/
http://clinicaltrials.gov/ct2/about-studies/learn
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