Cancer is one of the diseases that have long plagued humans. In the past decade or so, when it comes to cancer, many people think that human beings are sentenced to death, and because they are difficult to cure, they are terminally ill. The term "critical illness" became synonymous with cancer.
But not long ago, two research teams from the Dana Cancer Institute in Boston, USA, and the University of Mainz, Germany, announced a very happy news: in their research on patients with melanoma malignant tumors. The genetically modified vaccine developed in China was a great success in the first phase of the trial!
According to data provided by the US, four patients with melanoma malignancies participating in the treatment trial have fully recovered after genetically customized vaccination. The tumor cell content in the body is 0, and 32 have been tracked. There was no recurrence in the month, and the other two people did not disappear immediately after the tumor cells, but the tumor cells had disappeared with the help of other conventional means.
According to the data provided by the German side, a total of 13 patients who participated in the treatment trial, after vaccination, 8 tumor patients completely disappeared within 3 months, and continued to track for 23 months without recurrence, the remaining 5 As the cancer cells have spread severely, as of the publication of the study, two patients had a dilated tumor that shrank, and one patient completely eliminated the already spread tumor after receiving conventional adjuvant therapy.
Two related papers were published in the July 5 issue of Nature.
At present, the scientific community has unified opinions on how to clear cancer cells, and it is very concise and clear, that is, it locks and destroys the cells that have been mutated, and protects healthy cells. However, scientists have been painstakingly trying to achieve this goal.
The "tumor suppressor gene" in the cell has been mutated for various reasons, so that it can not inhibit the infinite amount of cell division and growth. Eventually, the cell will develop into a malignant tumor, and the position of the organ tissue which is originally composed of healthy cells can only be eaten. Work. Gene mutations make the surface of cancer cells theoretically have many abnormal proteins different from normal cells, and the immune system in the body should annihilate them according to the effector T cells.
However, due to the principle of “natural selection”, those surviving malignant cells are camouflaged and randomly generate new mutations. This made the immune system, which was so powerful that even the ones he played, began to be somewhat "incapable" and even "can" ignore some tumor cells. Moreover, many tumor cells gradually encroach on the original immune system, replacing the cells of the immune system with "oneself" and licking the entire immune system.
Although modern medicine can mature and activate the residual immune system, it will re-arm the immune T cells that are “turning a blind eye” to the tumor cells, and let them return to the battlefield with the “overnight roster”. However, this treatment method also has many defects. Such a lowering of the threshold of attack on immune cells can cause a variety of immune overexpression (or allergies) in people with poor immunity, as well as various strange inflammations. Among them, the most sought after CAR-T technology can only target some patients with "natural talents".
For such a problem, we can only give up the original results and take a different approach. Years of experience have led researchers to speculate that the presence of various variant proteins in tumor cells is not recognized by the immune system. It should be that the expression of these proteins is too small to alert the immune system.
Scientists have long been hoping to use these variant proteins to make antigens in vaccines, greatly increasing the antibody proteins secreted by human immune cells. The maturity of tumor gene cell sequencing technology makes this possible. As early as 2014, Nature published a paper like this. The author of the paper said that his research team has successfully used the tumor abnormal protein against mice to enhance the immune effect of the mouse itself. But for so many years, research on immune vaccines for human cancer has hit walls in most clinical trials.
The US team said that in order to create a personalized vaccine for different patients, it is necessary to first separate the patient's normal cells from the tumor cells for DNA sequencing to determine which different tumor cells have been mutated in different patients. The screened abnormal proteins were analyzed by a special algorithm which proteins were better recognized by the MHC proteins.
MHC proteins are involved in the recognition and presentation of antigens during the immune response. If an antigen that binds to an MHC protein is recognized by a T cell, the T cell will attack any cell containing the antigen.
After some hard work, the US team found more than 20 abnormal proteins for each patient as new antigens for vaccine development; the German team used a similar method to find more than 10 better combinations of MHC proteins in each patient. The new antigen is then produced into the corresponding RNA drug.
After removing the obvious tumor tissue by surgery, the two teams separately organized the patients for drug inoculation. Surprisingly, the vaccines developed by both teams stimulated the strong response of CD8+ T cells and CD4+ T cells in patients!
The CD8+ T cell mentioned above is an immune cell that specifically destroys a diseased cell. After being activated, the cell is capable of differentiating into a memory cell and an effector cell, wherein the effector cell is responsible for attacking the designated diseased cell. The memory cells will circulate in the body all the time. Once they encounter the same diseased cells, they will immediately divide and some of them will quickly transform into effector cells to start attacking. CD4+T cells are a kind of cell used for venting, specifically telling the characteristics of CD8+ T cells, that is, transmitting immune factors.
The final human experiment, as mentioned at the beginning, although two patients in the US team had recurrence, the memory cells that had been patrolling in the body immediately began to react and divide, and differentiated into effector cells to attack the recurring tumor cells. In the German team's experimental object, one of the dudes may be really "talented," and his cancer cells have mutated a gene that can suppress the expression of MHC protein by DNA, allowing tumor cells to escape the immune system. Monitoring. This is also a situation that cannot be ignored, and it is also the goal that they will study next.
The researchers pointed out that they have begun to consider the use of PD-1 inhibitors in conjunction with patient-specific personalized vaccines to determine if they can better contain tumor recurrence.
Although most scientists expressed great satisfaction with this achievement. But some tumor immunologists say that this can be said to be a good beginning, but because the experimental control object is really too few, only a few or a dozen are far from sufficient control effect, but this is definitely a Encouraging news.
Of course, this technology also needs great improvement and maturity, because it takes up to three months for each patient to customize a personalized vaccine. For many patients, this time is not delayed.
These two experiments have fully proved the feasibility of genetically customized vaccines. Many pharmaceutical manufacturers have started relevant research. With the next wave of clinical trials, more problems will be completely solved. .
