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Fail to recognize the great person ----History and Status of Immunotherapy

time:2019-01-13

The story was set in 846 AD, from the Seine river valley where the aggressive Norman army was preparing to attack Paris, France. The soldiers thought the French goddess waved, but it turned to be the black death who was quietly approaching.


At first, lots of pimples broke out on some soldiers’ faces. There was no beauty camera to help them cover pimples for seeking true love so that the soldiers suffered distress and indignation. They howled to heaven: if we can’t find girlfriends as true love, why shall we go to war?


However, punishment from God just started. Several days later, soldiers became extremely weak with high fever and lethargy bursting out among them and the pimples gradually beginning to suppurate.


What good could be done nearly 1,200 years ago? The helpless leader was forced to "eradicate" the disease with violence -- he ordered the burial of all the sick and those who came into contact with him. Though inhuman, it was the only scientific method at that time.


Disease swept across the world; on and off, for thousands of years, until, in the 18th century, it swept through Europe again, claiming lives of about 150 million people. For many nights, people looked up at the stars in the dark and prayed to god to end the endless havoc.


Dating back to May 17th , 1706, and Edward Jenner’ s waiting room is crowded with curious people. There was an eight-year-old boy in the doctor's office, enjoying a piece of candy. His name was Phipps. Jenner pricked the cowpox on the back of the milkman's hand, and the yellowish pus dripped onto the cut. A few days later, Phipps felt only a little discomfort and was soon relieved. Dr. Jenner then inoculated him with acne from people with the disease, which he did not contract. Ed Jenner saved many, many lives in this way, lighting up a world that had been dark for thousands of years with groundbreaking medical treatments.



Yes, you may be aware of it. It was smallpox.


What's interesting is that China's monarch of Qing Dynasty, a golden age, Hiowan Yei was also infected with smallpox in 1661. According to historical play in history, The Emperor Kangxi, seven-year-old Sue ma la gu came up with herbs to save small Lord Kang Ge.(As the writer of this article, I also marvel at the magic and great of the traditional Chinese medicine.) The lucky little master not only escaped from death, also became a generation sage-king, legendary emperor.(I can not help but think of a captious historian to point out the failure of portrait of pock on the face of Kangxi).


The disaster lasted for thousands of years, claimed hundreds of millions of lives and brought untold suffering and havoc to mankind. Fortunately, it reminded medical scientists to open up a new subject - immunology. People are beginning to realize that humans have a strong immune system and we just need a key to ignite it.


Since our immune system is so strong, then if it can play a role in cancer treatment?


In the early 1880s, a patient with malignant sarcoma contracted streptococcus pyogenes during an operation. Misfortunes never come singly. There were no antibiotics to fight with the disease, and patients had to rely on their own immune systems. Thankfully, after a few high fevers, not only did the streptococcal infection begin to subside, but the malignant sarcoma also miraculously disappeared.


This incident attracted the attention of William Coley, who began to try to treat malignant sarcoma with streptococcal infection and achieved unexpected results. This discovery made William Coley known as the "father of tumor immunotherapy" and officially opened the prelude of human tumor immunotherapy.


▲William Coley

PD-1 and PD-L1

In 1992, Japanese scholar Ishida discovered pd-1 from the apoptotic mouse t-cell hybridoma 2b4.11. Because it inactivates T cells, Ishida named it "programmed death receptor 1," or PD-1. However, subsequent studies have not confirmed a direct relationship between PD-1 and programmed cell death. PD-1 was dormant for many years, and it was not until the occurrence of autoimmune diseases was observed in PD-1-deficient mice that the function of PD-1 was gradually elucidated. In 2000, G. Freeman demonstrated that a novel B7 molecule binds to PD-1, thereby inhibiting the proliferation of T cells and the production of cytokines. The molecule is called PD-L1, or PD-1 ligand 1. Before that (in 1999), Chinese scholar Chen Lieping had reported that B7-H1 could synergistically activate T cells, while b7-h1 and pd-l1 had the same structure but different names. As the fame of PD-1 grows, so does the name PD-L1.


At present, there are 18 domestic enterprises whose PD-1 / PD-L1 monoclonal antibody project has been approved for clinical trials. In addition to bristol-myers squibb, which has been approved for listing this time, four other enterprises, including Merck, Hengrui, Cinda and Junshi, have submitted their listing applications, and all of them have been listed for priority review. Currently, there are five PD-1 / PD-l1 drugs on the market worldwide, including Opdivo of bristol-myers squibb (BMS), Keytruda of Merck, Tecentriq of Roche, Imfinzi of Astrazeneca, Merck and Bavencio of Pfizer.

CAR-T


CAR-T, the chimeric antigen receptor T cell, is one of the most effective treatments for malignant tumors. Like other immunotherapies, it works by using a patient's own immune cells to clear cancer cells, but this is a cell therapy, not a drug.


The treatments of CAR-T cells are as follows: white blood cells are isolated from the peripheral blood of the patient's T cells; use antibodies to activate T cells; T cells are genetically modified to express chimeric antigen receptors in vitro; T cells were cultivated and transformed in vitro. The genetically modified T cells were returned to the patient.


Cancer Vaccine


Cancer vaccines use cancer-related antigens to awaken the body's cancer-fighting immune system. An advisory committee of US Food and Drug Administration (FDA) has unanimously approved a proposal to allow Merck's cervical cancer vaccine to go on sale, marking a landmark new phase in the battle against cancer. In addition to HPV, quite a few vaccines have entered the clinic. Although some of them have not been approved by the FDA due to the huge clinical trial costs in various countries, they have been on the market for years enjoying reputation among patients, such as Hasumi Vaccine in Japan. Currently, there are four FDA-approved vaccines for cancer treatment, namely Gardasil and Cervarix for cervical cancer, hepatitis b vaccine for liver cancer and Provenge for advanced prostate cancer.


Opinion and expectations from the author:

Immunotherapy is the most promising killer that we have found to conquer cancer. It is now like a big tree which has grown from bud, showing its strong vitality. From advanced lung cancer to advanced breast cancer, cervical cancer and kidney cancer, immunotherapy is constantly changing the pattern of cancer treatment. In the following years, immunotherapy will continue to make breakthroughs. It is believed that immunotherapy will provide strong support for every cancer patient.