Use the body's own immune system as a cancer drug

Over the years, researchers have been eagerly focusing on the human immune system as a potential powerful weapon against cancer. However, when antibodies and immune cells in the body hope to find and destroy cancer, they also use the same method to eliminate bacteria and viruses. They want a theoretical home run, but its reliability has not been confirmed so far.

The reason for this result is related to the natural properties of cancer itself: cancer cells are not invaders, but healthy cells are irritating. Therefore, targeted therapy of tumors often means targeting innocent, healthy tissues. This is why cancer vaccines and immunization-based treatments ultimately have mixed success.

But last weekend, at the annual meeting of the American Society of Clinical Oncology (ASCO), researchers reported a promising medical advance: Dr. Kimberly Blackwell, director of the breast cancer program at the Duke University Cancer Institute, said: She and her colleagues used an innovative "smart bomb" therapy to successfully treat 991 women with advanced and metastatic breast cancer. The therapy uses a specific antibody to bind only to tumor cells, and then sends its explosive, a super toxin, to destroy them. This idea is very simple, Dr. Blackwell said, but it has been developed for more than ten years.

The key is to find a way to bypass healthy tissues encountered during transportation and directly deliver toxins to breast cancer cells. The answer is an antibody that recognizes a protein called HER2 located in the center of breast cancer. Once attached to HER2 in cancer, the antibody and its toxin can enter the cell, where the antibody is broken down and releases toxins that can destroy cancer cells.

In this study, this new drug called T-DM1, compared with the other two commonly used drugs, can delay the deterioration of the condition of women taking the drug for three months. For women using T-DM1, their condition did not develop further in 9.6 months compared to the 6.4-month suspension period in other groups. The data implies that T-DM1 can prolong the lives of women, but this study has not been conducted for a long time, and it is not enough to prove that they can survive.

Even if the drug is highly targeted, it is inevitable for many serious side effects of chemotherapy, including hair loss, nausea and vomiting.

"This is important evidence that this type of treatment has reached maturity," said Dr. Michael Linke, dean of the American Society of Clinical Oncology and professor of pediatrics at the Stanford University School of Medicine. "Historically, humans have discussed the use of antibodies as a special Treatment for cancer cells. We know that the human immune system is doing very well in this regard. The question is how do we make the immune system play an emergency role to achieve the purpose of anti-tumor. "

Previous attempts were to target the body ’s own immune system to fight cancer, including simply using antibodies to locate tumors, and then emit molecular signals to remind the killer cells of the immune system to perform their role-antibodies use multiple methods to destroy invading bacteria or various virus. But because cancer cells maintain their original health, antibodies ultimately cannot effectively raise vigilance against them.

What Dr. Blackwell and her team did was to bind a toxin bomb to their antibody, this is trastuzumab (the T component in T-DM1), also called trastuzumab, which is a A specific targeted drug for the treatment of HER2-positive breast tumors. Trastuzumab only binds to tumors with the HER2 protein—the type that all women in the study get. The other part of the drug, DM1, is a toxin and a linking molecule that smuggles DM1 around healthy cells so that it can play a positive role once it enters cancer cells. This also explains the good side effects of the drug. "Once this drug is put into use, this will be a great start in our future care of patients." Dr. Blackwell said.

In fact, there are other smart drug developments, including those that use the immune system in different ways. At the American Society of Clinical Oncology, researchers also presented data from Bristol-Myers Squibb's new therapy. They found a block protein called PD-1 in T cells, which is an important defense cell in the immune system. Many cancer cells can produce a molecule called PD-L1, which can bind to PD-1 and destroy the activity of T cells, which can make the tumor "invisible" to the body's immune system. Bristol's drug is an antibody that can record the molecular barrier that prevents PD-1 from being bound by PD-L1. In research, this drug can shrink melanoma, kidney and lung tumors that have been using other drug therapies. Because this drug is also targeted, researchers hope it will produce fewer side effects than other drugs. (

Blackwell also wanted to continue her research based on the immune route. She said that even the current immune system-based treatment method is far from bringing its advantages to the extreme: for example, drugs such as trenzumab can stimulate the immune system to a certain extent, and can compare Chemotherapy achieves better results. "We can fight cancer by stimulating the immune system with antibodies. This method can improve survival, but at the same time, we also use toxin chemotherapy to harm the immune system. This is a meaningless method," she said. "I think This is a potential reason. In the T-DM1 study, we saw such remarkable benefits, because we rely on the immune system, so that Tranizumab can be better played. "

She said that this idea tends to be immune-assisted cancer treatment, which enables the immune system to fight cancer without being weakened by chemotherapy. "I believe that the immune system of my patients can fight cancer as much as we help them fight cancer."

If this is the case, then the researchers ’focus will shift to more likely cancer-specific proteins, and then continue to develop antibodies to enable them to safely deliver targeted toxins to these proteins. In the end, Blackwell said, it may be possible to defeat cancer by using these elaborate molecular smart bombs without relying on general chemotherapy.

At present, there are certain restrictions on the use of drugs such as T-MD1: this new drug can only be used for patients with positive breast cancer HER2 indicators, excluding 80% of the total number. Scientists will continue to identify more proteins and molecules that can help cunning cancer cells avoid the body's immune system. Experts also hope to see more new therapies to overcome cancer problems. "I think we might use this technology for other tumors. This possibility is very exciting," Linke said. "This technology has ushered in its era."

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