Academician Wang has made great progress in the field of liver cancer treatment. She and her team discovered the cancer target GPC3, won national awards several times. After the interview, we summarized the material and learned about cancer research in detail.
As she said, this treatment had not received domestic approval as a formal treatment, and was now more at the stage of research and clinical trials, which led to a rather cumbersome procedure and certification processes for each case. On the one hand, this objectively restricted the spread of immunotherapy; on the other hand, this showed a national attitude towards immunotherapy. The government and medical center attached great importance to this treatment, because they believed it was important and useful. Such prudent attitude can provide a good protection for a developing treatment.
In addition, the country is ramping up research in this area. The ministry of science and technology has set up a special fund, and the Shanghai health and family planning commission has set up relevant projects as well. A better study environment was being built, which was believed could bring out promising and fruitful results.
New techniques, like CAR-T were still immature. When facing different cases, doctors need to adjust drug dosage in a wide range. The treatment effects on different patients also changed dramatically. This limited the spread of the treatment. Other problems including the drug specificity is poor and the efficiency of engineered cell getting in touch with cancer cell is low.
Topic 1: What is GPC3?
Wang: After years of researching, we confirmed the specificity of GPC3. Now, the monoclonal antibody of GPC3 has been prepared for diagnosis, and the patented kit has come into market. Besides, we cooperated with some labs to use GPC3 as a recognition site of CAR-T and carried out animal experiment.
For your project, there is one thing you need to pay attention. GPC3 is a protein anchored in the cytoplasm, which is mainly in the cytoplasm. A few GPC3 is anchored to cell surface, but the amount is too small to achieve ligand recognition. It must be an excellent work if you can achieve the membrane expression of GPC3.
Topic 2: How does CAR-T system work on GPC3?
Wang: CAR-T recognizes GPC3 by antigen presentation instead of ligand, so expression location is not a problem for CAR-T. However, it has some drawbacks. On the one hand, the therapy dose of CAR-T varies from person to person, which is an urgent issue for clinical application. On the other hand, as the recognition is mostly single target, the specificity is not so desirable, so researchers are searching ways to improve it.
In the blood, CAR-T makes sufficient contact with hematocytes, which enhances the specificity of recognition. However, in solid tumor, the contact is insufficient and the specificity is not so high. These will probably induce on-target/off-tumor effect or even error killing. Besides, dose control still remains a problem.
Topic 3: How do you think of our prject?
Wang: The idea is technologically workable and it’s great for undergraduate students to join a competition like iGEM, from which you can get research and public work experience. Although it’s a long way to application, demonstration of the concept “SwordS” is a meaningful step. After all, any scientific and technological achievements are not made in one step, but need to be explored for years.
Topic 4: Can you share your idea of cancer immunotherapy?
Wang: Cellular immunotherapy has not yet been approved in China and the experiment is under strict government regulation. So most of the experiment still remain in the animal stage. only a few cases of human experiments are carried out which should get permission from hospital ethics committee, patients and the National Health and Family Planning Commission.
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