Tumor vaccines use antigenic substances to activate the patient's immune system and induce the body's cellular immunity and humoral immune response, so as to achieve the purpose of controlling or eliminating tumors. Over the past few decades, scientists have been exploring ways to help fight cancer through vaccination, experimental vaccines designed to stimulate the body's own immune system to destroy tumors by injecting fragments of cancerous proteins found in tumors.
Recently, Liu Xiaolong's team from Mengchao Hepatobiliary Hospital of Fujian Medical University conducted research work on whether neoantigen-based vaccines can prevent postoperative recurrence in patients with hepatic cancer with vascular infiltration, and published important research results in the journal Molecular Cancer: personalized neoantigen-based vaccines can be used as a safe and efficient antioperative antioperative recurrence strategy for liver cancer, and the technology of tracking individualized neoantigen mutations in ctDNA is conducive to the practical application of personalized medicine in clinical practice. The newborn antigen vaccine is like a special squad lurking behind enemy lines, locating the position of tumor cells for the immune strike system, so that tumor cells have nothing to hide and can only be destroyed.
Research Results (Source: Molecular Cancer)
A total of 10 patients with HCC with vascular infiltrates were included in the study, and all enrolled patients underwent radical surgical resection after the diagnosis of HCC and underwent prophylactic TACE within 2 months. Tumor and perigma tissues were collected during the procedure for whole exome sequencing, a total of 780 non-homosexual cell single nucleotide variants were identified, and then 33.5% of the mutation expression in the total variant was further determined by transcriptome sequencing and identified as the source of neoantigens. Based on the neoantigen analysis of each HCC patient, the scientists synthesized 6-20 neoantigen long peptides (27aa) derived from somatic point mutations or RNA editing as vaccines, followed by mixing the prepared personalized neoantigen vaccine with ploy:IC (adjuvant) and injecting them in a "start-boost" mode for anti-relapse therapy in both armpits and groins of HCC patients.
Infusion protocol for individualized neoantigen vaccines in patients with HCC with vascular infiltration (Source: Molecular Cancer)
The results show that:
01
Vaccines have a high safety profile
No significant treatment-related adverse events were observed during vaccination, and no significant abnormalities were shown in blood routines or blood biochemical markers. Discomfort at the injection site that occurs after the vaccine is injected can also disappear quickly without additional treatment.
02
Vaccines prolong recurrence-free survival
Patients who received a complete neoantigen and developed an immune response had a significant increase in recurrence-free survival (RFS) compared with the control group, patients who received only the initiation phase of the vaccine or did not respond to the antigen vaccine (median RFS: 4.8 months vs 6.7 months vs 19.3 months, P=0.035).
03
Immunological and clinical response can be monitored
By tracking personalized neoantigen mutations in ctDNA in patients' blood, real-time monitoring and evaluation of immune and clinical responses in HCC patients was successfully achieved.
Therapy is still in the experimental stage The market demand needs to be met urgently
At present, neonatal antigen therapy is still in the laboratory stage, and there are no related products on the market at home and abroad. According to hospital experts with more than 10 years of experience in the biotechnology industry, it is estimated that newborn antigen therapy drugs need to complete clinical trials in at least 3 years, complete the review in 2 years, and take a total of 5 years to complete the drug listing process. In 2023, developed countries in Europe and the United States will take the lead in launching newborn antigen products, due to differences in regulatory systems and technical levels, China's local newborn antigen products will be launched in 2025. With the continuous increase in the number of new tumor patients in China every year, the demand for neonatal antigen therapy is growing rapidly, but at the same time, with the continuous maturity of the development of China's immunotherapy industry, the market standard management will be more stringent, and it is expected that the market size of China's newborn antigen will be rationalized after listing.
Table 1 Therapeutic tumor vaccines at the main clinical stage worldwide
(Source: Clinicaltrails.org, compiled by Southwest Securities)
Table 2 Clinical projects of tumor vaccines under research in China
(Source: CFDA, Southwest Securities)
According to the potential demand forecast for neonatal antigen therapy in China, it is expected that after the listing of Chinese neogen therapy drugs in 2025, the average price of a single course of treatment will be 600,000-800,000 yuan, and about 10,000 patients in the Chinese market will use neoantigen therapy in the first year, and the market size is expected to start from 6 billion yuan.
European and American enterprises take the lead in research and development Domestic enterprises actively layout
China's newborn antigen therapy industry is in the early stage of development, emerging enterprises continue to pour into the market, and began to layout in the direction of the whole industry chain, all links support each other, set collection, storage, scientific research and clinical industry chain has basically formed. The industrial chain of China's neonatal antigen therapy industry is mainly composed of three parts: upstream market participants include experimental reagent suppliers, medical instrument and equipment suppliers, and experimental consumables supply enterprises; the midstream main body is the production enterprise of nascent antigen therapy and medical institutions at all levels that provide clinical trial sites; medical institutions at all levels are also the main downstream places of the future neogen therapy industry, and after the new antigen therapy is listed, it provides disease treatment for tumor patients.
As a technology-intensive and talent-oriented industry, the new antigen therapy industry requires a lot of capital and human capital investment for independent innovation of products and technologies, and the risk is extremely high, and it is difficult for enterprises that lack technical foundation and financial support to gain a foothold in the increasingly fierce market competition. Overall, the global nascent antigen therapy industry is still in the experimental research stage and has not yet been released. According to the Clinical Trials Database in the United States, European and American companies led the research and development of neonatal antigen vaccines, with a total of 65 clinical studies, followed by Chinese companies, with a total of 13 clinical studies. The top three indications for neonatal antigen therapy were melanoma (12% of the total number of cases), breast cancer (9% of the total number of cases), and lung cancer (9% of the total number of cases). There are about 34 companies in the field of nascent antigen therapies internationally, and new companies are constantly emerging.
Chinese enterprises started relatively late, initially led by biotechnology companies with relatively abundant capital strength to carry out the research and development of nascent antigen therapies, such as Huada Gene, China's first nascent antigen therapy drug research and development enterprise under BGI Gene, with a cumulative financing amount of 100-200 million yuan. In addition, in the past five years, a number of start-ups in China have taken the gene sequencing link as the entry point to carry out neonatal antigen prediction. 70% of these start-ups are in the angel round stage, with a financing amount of about 10-30 million yuan, representing companies including Niuanjin Bio, Yuce Bio and Geyuan Zhishan. Overall, whether it is the amount of financing, technical characteristics, technical advantages, or the degree of opening up of the industrial chain, China's newborn antigen therapy enterprises have a certain gap compared with foreign enterprises, in addition, the hesitation of capital has also caused the slow development speed of the industry.
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Resources:
[1] Cai Z, Su X, Qiu L, et al. Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion. Mol Cancer. 2021 Dec 13;20(1):164. doi: 10.1186/s12943-021-01467-8. PMID: 34903219; PMCID: PMC8667400.