26 Mar 2012

The Gist

Human tumors transplanted into lab mice disappeared or shrank when scientists treated the mice with a single antibody, this according to a new study from the Stanford University School of Medicine.  A protein flag (CD47) on the cancer cells is masked, which protects them from macrophages and other cells in the immune system.  The findings were done with human breast, ovarian, colon, bladder, brain, liver and prostate cancer samples. 

Using the Immune System to Attack Cancer Cells with CD47

This is the first antibody treatment shown to be effective across a wide variety of human solid tumors along with the apparent cure in laboratory animals.  Investigators are eager to start what are called phase-1 and phase-2 human clinical trials within the next two years.

The professor of pathology Irving Weissman, MD, says that "Blocking this 'dont-eat-me' signal inhibits the growth in mice of nearly every human cancer we tested, with minimal toxicity."  Weissman directs Stanford's Institute of Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Research and Medicine at Stanford.  He goes on to say that it shows "conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy."

Another professor of biology at the Whitehead Institute for Biomedical Research in Massachusetts, who was not involved in this study, says "Mobilizing the immune system to attack solid tumors has been a longstanding goal of many cancer researchers for decades."

This research was published online March 26 in the Proceedings of the National Academy of Sciences.

There are immune cells called macrophages in the body that look for signs of trouble in the form of invaders or rogue cells.  Sometimes they latch onto the wrong target.  This is where CD47 prompts them to release cells they have grabbed by mistake.

Initial Findings Cured Cases of non-Hodgkin's Lymphoma

Weissman and his colleagues also showed that other types of cancer cells, like those of blood cancers like leukemia and lymphoma have found a way to use the "don't-eat-me signal" by utilizing CD47 on their own surfaces.  They found in 2010 that blocking CD47 with a specific antibody in combination with another to stimulate the macrophages, can cure cases of human non-Hodgkin's lymphoma in mice.  They later applied their findings to solid tumors.

Stephen Willingham, PhD and Jens-Peter Volkmer, MD are co-authors on this study with Weissman.  Willingham and Volkmer collected various samples of tumors ranging from ovarian, breast, colon, bladder, brain, to liver and prostate.  As a result they showed that nearly every human cancer cell they examined expressed CD47, usually on a higher level, around 3 times more on average, than non-cancerous cells.  There is also a correlation between having a lot of CD47 with cancer cells and shorter life spans than in people with similar cancers with less CD47.  This can be useful as a prognostic tool for doctors and their patients.

Solid Cancer Tumor Successes and Some Failures

Willingham and Volkmer implanted the tumor cells into matching locations in the bodies of mice.  They put breast cancer tumors in the mammary fat pads and ovarian cancer tumors into the abdomen.  They waited until the tumors were well established, usually around 2 weeks or more, then treated them with the anti-CD47 antibody.

Most of the established tumors began shrinking or disappeared within weeks of treatment.  One case resulted in the curing of five mice with the same human breast cancer cells.  After the cells were gone, they were monitored for four months, with no signs of recurrence.

The techniques applied did not work in every animal though.  For instance, one set of mice with breast cancer cells from one human patient experienced no benefit from antibody treatment.  Weissman stated "We need to learn more about the relationship between macrophages and tumor cells, and how to draw more macrophages to the tumors."  They have other theories on how to do this, including reducing the size of a tumor with surgery or radiation treatments before the antibody treatment would occur, consequently making the treatment more effective.  Or Weissman added, another option would be using a second antibody in addition to CD47 to further stimulate the ability of the macrophages or other immune cells to kill the cancer cells.

The Tech-Stew Take Home

As each day goes by, scientists and doctors are finding new ways to attack cancer cells, such as this antibody treatment and other methods like the engineered virus treatment.  The results of the antibody treatments are certainly promising and hopefully can be expanded into human clinical trials.  Clearly though, there is more work to be done to get a complete understanding of the mechanics of this new technique and perfect it for a variety of situations.  The research here will ideally lead to new hope and treatment options for cancer patients in the future.

Source:  Sciencedaily.com, med.stanford.edu


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