Can the acceleration of global tumor vaccine research and development be the gospel of conquering cancer?

In recent years, the research and development of tumor vaccines, which are expected to be used to prevent and treat cancer, has been increasing in the world, especially mRNA tumor vaccines. At present, the world is vigorously promoting the research and development of tumor vaccines, and the research and development of tumor vaccines by many teams in China is also making efforts. It is urgent to create a good environment for the research and development of tumor vaccines, and make full use of new technologies such as artificial intelligence to accelerate research and development.

Global Cancer Vaccine Development Speeds Up

As a new immunotherapy, tumor vaccine is a method that introduces tumor antigens, genes encoding tumor antigens, immune cells and molecules into the body to activate specific immune responses to kill tumors. In April 2010, the world's first related drug, Priwei, was approved for listing in the United States. The drug extracts the patient's own immune cells peripheral blood mononuclear cells, in vitro activation after reinfusion, for the treatment of asymptomatic or mild symptoms of hormone refractory advanced prostate cancer.

In recent years, especially since last year, with the help of mRNA vaccine technology, global tumor vaccine research and development has entered the fast lane.

In January 2023, the British government signed an agreement with Germany's Bairntek to obtain trials of personalized mRNA therapies including tumor vaccines as soon as possible. In December 2022, Modner and Mercadon announced that their mRNA vaccine under development combined with PD-1 therapy would reduce the risk of recurrence of high-risk melanoma by nearly half. The vaccine had earlier been granted breakthrough recognition by FDA of the United States and entered the accelerated review channel. Companies in France and Norway are also accelerating the development of cancer vaccines.

The research and development of a variety of tumor vaccines in China is also making progress. In January 2022, the mRNA personalized tumor vaccine of the microorganism was approved for Phase I in Australia, becoming the first domestic mRNA tumor vaccine approved for clinical use in the world.

In March 2023, "LK101 Injection" independently developed by Beijing Likang Life Technology Co., Ltd. became the first personalized nascent antigen mRNA tumor vaccine approved for clinical use in China. In October, Zhifei Biology, Sun Yat-sen University and Sun Yat-sen University Cancer Prevention and Treatment Center announced a cooperative research and development of EB virus vaccine, aiming to promote the early prevention and treatment of EB virus-related malignant tumors and chronic diseases. In addition, personalized tumor vaccines from companies such as New Anjin Bio, Xinhe Bio, and Condesai Medical have also announced that they have received applications for clinical trials in 2023.

In recent years, Chinese scientists have targeted basic scientific research issues related to tumor vaccines, intensified research efforts, and made some progress. For example, in December 2023, the team of Sun Yat-sen Memorial Hospital of Sun Yat-sen University published a paper in the international top academic journal Nature, and found that circular RNA can encode tumor-specific antigens, which is different from previous tumor mutation antigens and tumor-related antigens. It has the advantages of wide expression and high immunogenicity in most patients. The T4 ligase method used in the synthesis of circular RNA in this paper is the most classic and direct method, stable and reproducible, the team has mastered a more efficient intron self-splicing system synthesis strategy to cope with the industrial synthesis and transformation of future tumor vaccines.

In December last year, Zhao Xiao and Nie Guangjun, researchers at the National Nanoscience Center, proposed a "peri-vaccine" immune pre-excitation strategy-using bacterial-derived nanovesicles to strengthen the body's immune system function, thereby enhancing the effect of subsequent tumor vaccine immunotherapy.

Cancer vaccine development still faces challenges

Tumor immune regulation is an extremely complex process and is interfered by many factors. Therefore, even though scientists have worked hard for many years, the development and application of tumor vaccines are still not as expected. Many industry experts said that the global tumor vaccine research and development still need to break through a series of difficulties.

Xia Ningshao, academician of the Chinese Academy of Engineering and professor of the School of Life Sciences/School of Public Health of Xiamen University, said that the mechanism of action of cancer vaccines is to enhance the recognition and presentation of tumor-associated antigens or tumor-specific antigens by the body, thereby activating the body to produce specific attacks and Destroy the immune response of malignant tumor cells, and generate a systematic anti-tumor immune response through the adaptive immune response. The screening of tumor antigen molecules is a major challenge in the development of cancer vaccines.

Hui Aimin, vice chairman of the China Biopharmaceutical Industry Chain Innovation and Transformation Consortium and chairman of Huichengqi Pharmaceuticals, said that the current cutting-edge mRNA tumor vaccine technology started late in China, and the underlying technology and process of mRNA vaccine, including antigen design and antigen selection of tumor vaccine, are all in the exploratory stage.

"There are very few people who have actually done mRNA tumor vaccines in the first line of China, especially the lack of personnel and talent reserves who really understand mRNA vaccine technology and have experience in successfully developing innovative drugs and putting them into the market." Back to Aimin said.

Some people in the industry also said that the founders and teams of some mRNA companies are more from the development of dosage forms and production processes, and lack a thorough understanding of bioinformatics and immunology, which has become the main problem in their current talent team building.

Global regulatory policies for cancer vaccines are also being explored. For example, the FDA of the United States first approved the listing of the world's first tumor vaccine in 2010, and then began to continuously improve the regulatory policies related to tumor therapeutic vaccines. During the new crown outbreak, the "green light" of mRNA technology in many countries further promoted the hot field of tumor mRNA vaccine research and development.

Suggest using new technology to accelerate tumor vaccine development

In an article published at the end of last year, the team of Professor Chunyan Dong of Tongji University believes that future progress in the clinical efficacy of therapeutic tumor vaccines will focus on several key areas, including identifying immunogenic neoantigens, optimizing vectors and delivery platforms, and overcoming immunosuppressive tumor microenvironments. Next generation sequencing, increased computing power and advanced algorithms significantly make it possible to identify highly immunogenic neoantigens. Ongoing research is dedicated to improving vaccine technology, including exploring different expression patterns, improving co-stimulatory components, and identifying suitable primary reinforcement methods.

At present, mRNA vaccine is the mainstream cutting-edge technology used in global tumor vaccine research and development. Industry insiders suggest that the technology of mRNA vaccine should be taken strategically at the national level, including not only mRNA tumor vaccine, but also mRNA infectious disease vaccine.

Interviewees said that scientific and technological research projects should not only be given to universities, research institutes, and head pharmaceutical companies, but also fully support high-level small and medium-sized biopharmaceutical companies. From the perspective of the global pharmaceutical industry, most of the key technological breakthroughs are achieved by small and medium-sized biopharmaceutical companies, such as Bairntek and Modena, which have gained global attention in the development of the new crown vaccine.

Zeng Musheng, deputy director of the Cancer Center of Sun Yat-sen University, suggested that the country not only standardizes the management of tumor vaccine research and development, but also contributes to innovation. There are also experts who suggest that high-level scientific research teams should be provided with opportunities for dialogue with high-level government and national experts, so that truly capable people can receive corresponding support.

In the development of tumor vaccines, antigen selection is a key. Hui Aimin said that humans have a huge genome, and a tumor may have hundreds of 10. genetic mutations. It is extremely difficult to choose which mutation as an antigen, and the global industry is still exploring. At present, the use of artificial intelligence, big data model to accelerate antigen selection, optimization for mRNA tumor vaccine research and development is a "must option", the industry should actively use domestic artificial intelligence, supercomputing and other advantages of resource conditions, accelerate tumor vaccine research and development.