Liu Mi is currently a distinguished professor in the Department of Pharmacy at the School of Pharmacy, Suzhou University. Recently, he and his team have developed a nano vaccine, which has a prevention and recovery rate of 99.99% and 70% for lung cancer and melanoma in mouse cancer models, respectively.
He told DeepTech that his preliminary plan for clinical application is to take out the tumor tissue of the patient, send it from the hospital to the pharmaceutical factory, prepare the vaccine, and then send it back to the hospital, where the patient can be vaccinated directly. Compared to technologies such as CAR-T, nanovaccines are not only more convenient but also cheaper in price.
On September 18th, a related paper titled "Immunotherapy and Prevention of Cancer by Nanovaccines Loaded with Whole Cell Components of Tumor Tissues or Cells" was published in Advanced Materials.
Previously, only a very small number of cancer vaccines were successfully launched
In recent years, research on cancer immunotherapy has been very hot. In 2018, two scientists were awarded the Nobel Prize for their achievements in cancer immunotherapy, which involves immune checkpoint inhibitors.
Almost every human body has a certain number of cancer cells, but the vast majority of people do not develop cancer. The main reason is that the immune system plays a "police" role in the body, constantly monitoring all cells. Once cells undergo cancer or mutation, the immune system will eliminate the cancer cells. Therefore, the immune system is also an inherent protective system in the human body.
However, in some cases, once the immune system's monitoring function is disrupted and cancer cells cannot be effectively controlled, they will undergo rapid proliferation, leading to cancer.
From an immunological perspective, the human body has many mechanisms to control cancer, which work by activating the immune system.
Using driving as a metaphor, in the immune system, braking is equivalent to an immune checkpoint, and releasing the brake is equivalent to using immune checkpoint inhibitors. When the immune system attacks abnormal cells such as cancer cells, in order not to harm other cells, it will promptly "brake", which is also an important step in the process of cancer occurrence.
In 2018, the two scientists who won the Nobel Prize for their achievements in immune checkpoint inhibitors were equivalent to releasing the brakes. Cancer vaccines can act as a throttle, activating the human immune system.
When releasing the brake, adding the throttle will have a better effect. Injecting a cancer vaccine is equivalent to stepping on the accelerator to make the car run faster, thereby better and faster identifying and killing cancer cells. This is also from a macro perspective, cancer vaccines and immune tests during cancer immunotherapy
Figure | Preparation of nanovaccines and brief schematic diagram of tumor specific immune response induced by nanovaccines (source: interviewee)
In previous studies, some scientists directly lysed tumor cells, isolated water-soluble components, and injected them directly to stimulate the immune system, but this method has not been clinically effective. The components obtained after direct lysis and separation are water-soluble, so they cannot penetrate the cell membrane or enter antigen-presenting cells.
During the activation process, it is necessary to first enter antigen-presenting cells and then activate T cells to activate the immune response. In order for a substance to enter cells, it must be lipophilic because the cell membrane is lipophilic. At this point, water-soluble proteins or peptide components cannot enter the cells, and as they cannot enter the cells, they cannot effectively activate the immune system.
As the most loyal and important antigen-presenting cell in the immune system, it particularly enjoys phagocytosing nanomaterials, especially those between 100-500 nanometers. The human body itself has many cell secreting particles, and these secreting particles that communicate between various cells are all nanoscale, which can be engulfed by the human immune system.
Based on this, Liu Mi made the nanovaccine into a size of about 300 nanometers, which can simulate the secretion particles in the body in terms of volume. Due to the special preference of anti-cancer presenting cells for phagocytosis of nanovaccines, nanovaccines can release antigens and activate the human immune system after entering the cells.
If it is not reorganized into nanoscale sizes, although the antigen still exists, it cannot be effectively engulfed by cells, thus unable to activate the immune system. Originally, simply lysis of cancer cells, extraction of components, and activation of the immune system were ineffective because antigens had no effective pathway to enter cells.
Because the process of activating antigens is complex and requires multiple signals to exist simultaneously, the addition of adjuvants in nanovaccines can effectively enhance the efficiency of antigen activation of the immune system.
If there is only antigen, the activation effect is cross. So, Liu Mi co delivers antigens and adjuvants to enhance the activation effect of the nanovaccine, which is equivalent to making its memory more profound, so that its immune response will be stronger. After completing this vaccine, he and his team conducted preventive and therapeutic experiments on mice.
In preventive experiments on mouse models, nanovaccines can achieve 99.99% prevention of lung cancer and approximately 70% prevention of melanoma. In the therapeutic test on the mouse model, the nano vaccine has good therapeutic effect on melanoma and triple negative breast cancer, but the therapeutic effect on melanoma is better than that on triple negative breast cancer.
Figure | Experimental results of nano vaccines for preventing lung cancer and melanoma (source: respondents)
As long as the cancer tissue is extracted, it can be made into a nano vaccine. In order to verify that this method can be used for the vast majority of cancers in the experiment, they selected several different types of cancer.
I chose lung cancer because it is more common in China. Melanoma and breast cancer were chosen because it is easier to obtain tumor tissue for the onset of these two cancers.
The difficulty of extracting tumor tissue varies, for example, melanoma is actually a type of skin cancer that is located on the surface of the skin and is easier to remove. At present, melanoma can be treated surgically. When the tumor block is removed, it may recur or metastasize. Sometimes, new tumors may slowly grow around the tumor that has not been completely removed.
So, after cutting out the tumor tissue, it can be made into nano vaccines and injected into the patient's body, which can prevent recurrence and metastasis. Moreover, if the results of this study are combined with PD-1 antibodies, a synergistic effect can be achieved, and patients can also achieve a higher cure rate.
Figure | Experimental results of nanovaccine in treating melanoma in a mouse model (source: respondents)
Liu Mi stated that if a drug under development is to be marketed or commercialized, the simpler the ingredients in the vaccine, the better, making it easier to prepare and control its quality. Therefore, this nano vaccine was designed using all FDA approved medicinal materials, ensuring safety and fast preparation.
If not freeze-dried, the preparation can be completed in one day. If freeze-dried, it takes about three to four days to complete the preparation, which is also beneficial for cancer patients to quickly obtain the required vaccine drugs.
Figure | Analysis of T cells and tumor microenvironment in mice treated with nanovaccines (source: respondents)
Currently, Liu Mi has applied for 10 patents. Among them, five are international invention patents and five are domestic patents. The development process of a drug is lengthy, and its effectiveness in mouse experiments is only the first step. Multiple clinical trials need to be conducted after completing various applications to prove that the drug is truly effective.
At present, we have only completed the first step, and there is still a long process ahead. At the same time, he is also in contact with pharmaceutical companies, hoping to carry out clinical trials as soon as possible.
Figure | B cell aggregation and tertiary lymphoid structure formed by multiple immune cells in the tumor microenvironment of melanoma treated with nanovaccines in mice
Liu Mi told DeepTech that he graduated with a master's degree from the School of Pharmacy at Peking University in 2010 and a doctoral degree from the Department of Pharmacy at ETH Z ü rich in Zurich in 2014. At the end of 2014, he came to the Department of Immunology at Harvard Medical School for postdoctoral research. Four years later, at the end of 2018, he joined the Department of Pharmacy at Suzhou University School of Pharmacy as a distinguished professor and doctoral supervisor.
He stated that Suzhou's urban planning and management concepts are advanced and very livable. In addition, the School of Pharmacy at Suzhou University has continuously introduced talents in the field of pharmacy in recent years, and the Suzhou Municipal Government is also very supportive of the development of the pharmaceutical industry. Suzhou is expected to become a gathering place and center of the pharmaceutical industry in the future.
