[Perspectives of Traditional Chinese and Western Medicine]Immunotherapy using two drugs, PD1 and CTLA4, to treat melanoma

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Text ◆ Su Ziqian (clinical oncologist/TCM physician)

Melanoma is a type of skin cancer, but this cancer is relatively rare, especially in Hong Kong.

In Western societies, especially in Queensland, Australia, the incidence of melanoma is very high. Mainly because Westerners, especially white people, are damaged by ultraviolet light from the sun. Long-term exposure to the sun can damage the genes of skin cells and produce melanoma.

(Hong Kong News) This type of cancer is not common in Asians. In many cases, the disease occurs under the nails of the toes or on the soles of the feet, where the sun does not reach it. This aspect is very strange. There is no reason for these places to be exposed to a lot of ultraviolet light, but it has been found that the disease in these places is particularly likely to be related to some genes.

Immunotherapy for one year after surgery

Melanoma, as the name suggests, is really a black color in most diseases. Because this kind of cancer precipitates some melanin, most patients only have a dark patch of skin with no pain or itching and no feeling. They think it is just a bruise caused by an accidental collision, or they think it is just some benign black spots. Many times after It takes some time to diagnose.

Early treatment must be mainly surgery, and sometimes even local lymphadenectomy is required. If lymphatic spread is found after surgery, immunotherapy should be performed one year after surgery to reduce recurrence.

It has been mentioned many times before that the function of immunotherapy is to stimulate the body’s lymphocytes, allowing the lymphocytes to recognize cancer cells and launch an immune attack. Immunotherapy can be said to be the backbone of the treatment of melanoma, because chemotherapy has little effect on melanoma and is not very effective. A small number of melanomas may have special genes, such as BRAF gene mutations, which can be treated with single-target or dual-target drugs. . But immunotherapy is always the backbone of the treatment of this disease, and even patients who have spread can have a chance to be cured.

As for patients who have spread, when using immunotherapy, they should also use one or two immunotherapy drugs together, and use two immunotherapy drugs to treat them at the same time, that is, use PD1 and CTLA4 drugs at the same time, both of which are injected The drug also stimulates lymphocytes, but the point of action is somewhat different.

Continuously effective and does not require long-term injections

There are actually two aspects of work for lymphocytes to be stimulated. The first aspect is in the lymph nodes. In the lymph nodes, the lymphocytes will meet macrophages that have traveled back from other places. After these macrophages come into contact with the expansion of cancer cells, they will educate the lymphocytes as they move to the lymph nodes. Simply put, these macrophages will stimulate the lymphocytes and let the lymphocytes know to attack the cancer.

To put it simply, the macrophage pack is like a vanguard, returning to the base camp to tell the lymphocytes which one is the enemy outside and who should be chased and fought. The communication and stimulation between macrophages and lymphocytes is stimulated by CTLA4 drugs.

The stimulated lymphocytes will travel throughout the body in search of cancer cells. After seeing the cancer cells, the lymphocytes will stick to the cancer cells. Many times, there is a surface substance such as PDL1 on the surface of the cancer cells, which is a deceptive signal. It is used to tell lymphocytes that melanoma is a normal cell in your body and please do not attack it.

PD1 immunotherapy drugs are designed to block these deceptive signals, allowing lymphocytes to be activated to mount an immune attack on melanoma.

Therefore, the use of dual immunotherapy works in these two places at the same time to achieve a synergistic effect. It should be noted that even if it is dual immunotherapy, two drugs are usually used together, and only 4 injections are given. After 4 courses of treatment, only PD1 immunotherapy is usually performed.

The reason why it is not necessary to take the two drugs together for a long time is mainly because once the immunity is stimulated, it can continue to be effective. In many cases, long-term injection of drugs is not needed. On the other hand, because the immune side effects of using the two drugs together are severe, safety is a problem if used for a long time.

However, research in recent years has found that using a low dose of CTLA4 immunotherapy, which is only one-third of the original dose, can achieve similar immunotherapy effects, and the toxicity is greatly reduced, so many people also use low doses of CTLa4 Drugs.

Lymphocyte inactivity affects efficacy

Of course, the price of using the two drugs together is also very expensive, especially if the original dosage is used, not every patient can afford it. But in any case, although immunotherapy has a certain effect, some patients have no effect at all after being injected with immunotherapy, or they may develop drug resistance. Why exactly is this happening? Why can’t the body’s lymphocytes play an immune role?

There are many reasons, one of which is insufficient lymphocyte activity. It turns out that the microbiota distribution of bacteria in our large and small intestines can affect the effectiveness of immunotherapy. There are actually many lymphocyte tissues in the large and small intestines. It can even be said that the large and small intestines themselves are the largest immune organs. By using probiotics to regulate the distribution of bacteria in the large and small intestines, the body’s immunity can be improved, allowing the effectiveness of immunotherapy to be unleashed.

Good bacteria in your intestines are key

Fecal transplants work

Is there any evidence for this concept? A few years ago, someone conducted an experiment and found that two groups of mice all developed melanoma at the same time. One group was effective in immunotherapy, while the other group was ineffective.

If the same immunotherapy is continued and the feces of the effective group of mice are fed to the ineffective group of mice, some of the ineffective group of mice will actually become effective!

It can be seen that changing the composition of bacteria in the large and small intestines has an important impact on whether immunotherapy can work.

In the past year, it was also reported in “Nature” that the same method was used on the human body to obtain very similar results! For the patients in the invalid group, stool samples from the effective patients were transplanted. Twenty percent of patients actually regained the effectiveness of immunotherapy! The results are encouraging.

Traditional Chinese and Western medicine complement each other

However, fecal transplantation is not a very convenient method that is acceptable to everyone. What is more important is to understand which beneficial bacteria are beneficial to immunity. So as to carry out some probiotic drug treatment.

On the other hand, even if lymphocytes are sometimes stimulated, sometimes they are unable to enter and approach cancer cells due to local obstruction of some blood vessels. When lymphocytes cannot get close to cancer cells, even the most active lymphocytes will be of no use. Therefore, in Western medicine treatment, some anti-angiogenic target drugs are sometimes used together with immunotherapy.

It was found that the two complement each other, and this method is already a basic therapy in the treatment of other cancers, such as kidney cancer. Research in melanoma is ongoing.

In fact, this aspect is very similar to the concept of traditional Chinese medicine. The so-called assisting righteousness in traditional Chinese medicine is to let the body’s own righteousness defeat cancer cells. Some traditional Chinese medicines that replenish qi and strengthen the spleen can stimulate the activity of lymphocytes in the laboratory.

Most patients have qi stagnation and blood stasis

On the other hand, more people know that Ganoderma lucidum and Yunzhi also play a little role in the laboratory. In addition, Chinese medicine believes that many patients with melanoma have the so-called qi stagnation and blood stasis, which means that the blood qi does not flow smoothly and is blocked, so that the body’s righteous energy cannot reach the place where the cancer cells have spread.

Therefore, when replenishing qi, you should also give some drugs that promote blood circulation and remove blood stasis, combined with Chinese medicine that relaxes the muscles and activates collaterals, so that the healthy qi can reach the patient.

In terms of treating melanoma, Chinese and Western medicine do have a little bit in common.

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