Macrophage "criminal record" so much, Professor Penn can rest assured that it went to the front line anti-cancer?

On July 18, 2017 / d MaiKe eMedClub / - currently, based on the engineering of T cell CAR - T therapy for already listing of haemal tumour, but in the treatment of solid tumor, CAR - T therapy seem powerless.

Because T cells can't infiltrate into solid tumors, there's no way to play it.

But macrophages are different, and it can easily permeate diseased and damaged tissues, including tumors.

That said, a lot of research has found that macrophages don't have much to do with destroying cancer cells.

Who asked the creator to make cancer cells so advanced that it would release the same signals as healthy cells (Don't eat me!).

To avoid the attacks of macrophages.

With CD47 and SIRP alpha, macrophages do not consume tumor cells;

CD47 is bound by antibodies, and tumor cells are swallowed

(photo courtesy biodiscover.com)

As human health guard, the main task of macrophages is to eat cells that are harmful to humans.

But studies have shown that there seems to be something wrong with macrophages inside the tumor tissue, and the more tumors that macrophages have, the worse the prognosis.

After through a lot of research, the scientists found that macrophages not only prevent such as T cells attack tumor cells, nourish himself also secrete growth factor of tumor cells, promote the formation of tumor blood vessels, leading to the spread of cancer cells to metastasize.

Despite the number of "precurs", researchers at the university of Pennsylvania have devised a way to engineer macrophages to eliminate solid tumors.

Macrophages binding cancer-specific targeting antibodies,

Phagocytosis in mouse models (image source Discher Lab)

The university of Pennsylvania school of engineering and applied science, Pennsylvania perelman medicine, physics, science cancer center researchers design of the engineering macrophages, natural is different from ordinary macrophages.

It has the ability to distinguish between healthy cells and tumor cells.

With superpowers, engineered macrophages can cycle through the body of mice, invade solid tumors and specifically devour human cancer cells.

Based on cancer cells evade mechanism, Discher laboratory focus on the can to respond to the protection mechanism of macrophages on the surface of the protein, research by the Pennsylvania department of chemistry and molecular engineering Dennis e. Discher, Robert d. professor Bent and the medical graduate student Cory Alvey joint ownership.

Alvey said: "our new method derived from human bone marrow donor learn young and aggressive macrophages, and eliminates the tumor cells to prevent the security barrier being swallowed. Through the redesign the macrophages, the combination of cancer-specific targeting antibodies, then these macrophages into solid tumors, and promote human tumor fade quickly, and will not produce any toxic effects can be measured."

The Discher lab has shown that protein on a human cell called CD47 ACTS as a "self-marker" by interacting with the protein SIRP alpha on the surface of macrophages.

When SIRP is combined with CD47 on cells, it protects cells from phagocytosis, which also includes tumor cells.

Knowing the mechanics of macrophages sucking up tumor cells, it's easy to see that tumor cells are doomed if they block the path of CD47.

The researchers also saw this, of course, in the process of experiment, blocking CD47 with SIRP alpha treatment on mice as the experimental model to observe the treatment effects on tumor size.

But the result was not the way it was thought, which led to a reduction in blood cells in mice.

And in the experiment, some mice died of anemia, and some mice died of autoimmune diseases caused by a lack of CD47.

Here, we engineer and then systemically inject highlyphago - cytic marrow - derived macrophages that have both SIRP alpha inhibition and tumor targeting Abs pre - the loaded into Fcreceptors (image source Discher Lab)

In order to avoid these safety problems, and to maximize the potential of the tumor to be treated.

Alvey, and his colleagues collected from human donors and donor mice fresh young macrophages, in its SIRP alpha directly on the surface of the block colleagues also injected with the targeted cancer cells can be all kinds of antibody, this may help to activate macrophages into the tumor.

Surprisingly, though the macrophages can circulate throughout the body, the study found that they only congregated in the tumor and phagocyte.

After two injections, the tumor cells shrank by 80 percent.

It is important that this method does not affect the function of blood cells, thus indicating that this method is safe.

So far, Discher says, the safety may be the relatively small number of engineered macrophages that are injected, and they are all inside the tumor, and are separated from normal cells.

The study also found that after about a week, when the macrophages that gathered at the tumor cells after the injection stopped eating, they were injected again, still able to safely weaken the tumor cells.

At present, the researchers have been quite clear about the effectiveness of these engineered macrophages.

But the key question is how to maximize the effects of cancer and minimize side effects?

The next step, Discher says, will be to focus on finding more accurate cancer cell targets and extending the use of modified macrophages.

T-cell immunotherapy is "hot" and immunotherapy in macrophages is also "working"!

The other wave of cancer immunotherapy is coming, anyway.

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