Scientists Have Pried The Bone Of Cancer Treatment

- Jan 06, 2020-


Cancer is one of the most important causes of death in the world, which kills countless people every year. In the treatment of cancer, although mankind has made a series of breakthroughs, there are still many hard bones. A paper published today in science, a leading journal, offers a whole new combination of therapies. It may bring new breakthrough for cancer treatment!


A hard bone to chew


We know that cancer can be simply divided into two categories: one is blood cancer, leukemia and lymphoma belong to this type of cancer; the other is called "solid tumor", that is, there are actual tumors. Generally speaking, lung cancer, liver cancer and gastric cancer are solid tumors.


In the treatment of blood cancer, a revolutionary therapy called "car-t" was born a few years ago. The treatment is to isolate immune "T" cells from the patient's body, and then install them with a kind of navigator called "CAR" through gene editing. The Navigator allows immune cells to recognize cancer cells and attack them. Car and t of "car-t" therapy come from this.


In many blood cancer treatment, CAR-T therapy has achieved very good results. One of the first girls to receive CAR-T therapy was Emily Whitehead. Originally, because of leukemia, she had no cancer for 7 years after participating in the clinical trial of CAR-T therapy! With the help of immune cells, the little girl's leukaemia has become traceless, equivalent to being "cured".


For many other blood cancer patients, car-t therapy can also bring miracle of life. At present, the FDA of the United States has approved two CAR-T therapies, and more car-t therapies are expected to come out this year to benefit patients.


However, for solid tumors, the role of car-t therapy has been very limited. Many scientists point out that this is due to the lack of "navigation address" on solid tumors that can be recognized by immune cells. If you can't find cancer cells, you can't attack them. If the navigation address is set to be fuzzy, the immune cells will mistakenly attack other normal tissues and organs. In the treatment of cancer, this is a hard bone to chew.


Cancer specific signals

In a paper published online today in science, scientists have found such a "navigation address" that only belongs to cancer cells. This address is called CLDN6. It is a protein expressed on the cell surface, which can make the cells stick together tightly. Interestingly, CLDN6 is particularly abundant in the process of embryonic development, but in adulthood, its content will drop sharply. The researchers analyzed more than 50 different tissue types in healthy adults and found no CLDN6 in them.


Interestingly, the level of CLDN6 is particularly high in solid tumors such as ovarian cancer, lung cancer and uterine cancer. That is to say, in adults, if the immune cells can navigate to the location of CLDN6, they can probably attack the cancer cells behind the address.


That's what researchers do. They have developed a new car-t therapy, in which the navigator is aimed at CLDN6. In vitro experiments, scientists confirmed that this treatment can effectively kill cancer cells with CLDN6. What's more, it will not "go astray" and "cross the door" to the cells expressing cldn3, cldn4 and cldn9, so its attack on cancer cells is very specific.


If the CLDN6 "doorplate" on cancer cells is removed through gene editing, the cell therapy will lose the ability to attack cancer cells. These results also show that it is indeed designed by the researchers to attack cancer cells by looking for CLDN6.


In the mouse model with large ovarian cancer tumor, the car-t therapy has achieved obvious effect. After only two weeks of treatment, all the tumors in mice showed complete regression. In contrast, mice in the control group had tumors that still grew crazily.



Improve the anti-cancer effect

The researchers were not satisfied with the results. On the contrary, they realized that in the treatment of blood cancer, immune T cells can touch a large number of cancer cells' surface expression "doorplates", so they will expand a lot. In the treatment of solid tumors, the immune T cells do not have too much chance to contact the "doorplate", which will limit their number, thus limiting their efficacy.


To this end, researchers have developed a "cancer vaccine". In this study, the scientists put the information (RNA expressing CLDN6) that can make "doorplate" into a small ball called "liposome" and introduced it into the lymph system of mice. Sure enough, with the help of the vaccine, immune T cells expanded in large numbers. This can also be understood as the rapid growth of the anti-cancer immune cell army.



With the increase of the number of immune cells, the anti-cancer effect of this therapy has also improved. If only receiving car-t treatment, it can only delay the growth of tumor in mice with refractory lung cancer. Less than 20 days after treatment, half of the mice died of cancer. On the contrary, if both car-t therapy and RNA vaccine were injected at the same time, after 25 days of treatment, all mice still survived and the tumor volume decreased.



In general, this paper published in science strongly responds to the problem that car-t therapy is difficult to treat solid tumors. At the end of the paper, the researchers pointed out that this research has provided us with a solid foundation, so that we can better gnaw down the hard bones of other cancer treatment paths, and bring benefits to patients around the world as soon as possible! ( from, compiled by