Nuowei Bio Announces Breakthrough in Chemokine-Enhanced mRNA Cancer Vaccine Technology with Publication in Molecular Cancer (IF=37.3)

Recently, Dr. Hailong Qi, co-founder and CTO of NEWISH, and Academician Jiandong Jiang jointly published a research paper titled "Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response" in the internationally renowned academic journal Molecular Cancer (2022 IF: 37.3, Chinese Academy of Sciences Medicine, Oncology, Biochemistry and Molecular Biology all ranked Zone 1, JCR: Q1).

The study identified a series of chemokines through large-scale in vivo screening, which significantly enhanced the cellular immunity induced by nucleic acid vaccines. Among them,The paper particularly focuses on the most potent chemokine CCL11 and elaborates on how it significantly enhances the anti-tumor immune therapeutic effect of nucleic acid vaccines by improving the differentiation of stem memory T cells.。

The paper further points out,Enhanced strategies utilizing chemokine targeting of antigen-presenting cells (APC) not only boost the ability of nucleic acid vaccines to activate antigen-specific T cells but also aid mRNA vaccines in achieving the eradication of high-burden tumors.. This groundbreaking discovery will provide new ideas and methods for overcoming tumors, marking a new milestone in the development of mRNA tumor vaccine technology.

The STARi nucleic acid drug development technology platform, featuring the development of chemokine-enhanced nucleic acid vaccines, was jointly created by NEWISH and Academician Jiang Jian Dong from the Chinese Academy of Medical Sciences. The STARi platform aims to develop a new generation of nucleic acid drugs, providing innovative and groundbreaking therapeutic vaccines for patients worldwide to meet unmet clinical needs.

Researchers first relied on a mature DNA drug development and evaluation platform to construct fusion plasmids by individually combining all 47 human chemokines with antigens, followed by immunizing mice and assessing their cellular immune responses (see Figure 1). Through preliminary screening, six chemokines that significantly enhanced specific T-cell immune responses were identified. These six chemokines were further evaluated for their anti-tumor immunotherapy effects in tumor models. The results showed,The tumor vaccine prepared by fusing CCL11 achieved 100% tumor clearance in all mice (n=8) in the treatment group, demonstrating strong therapeutic effects. The survival curve also showed a 100% survival rate in the mice of the CCL11 fusion treatment group.(see Figure 2).

Figure 1: Chemokine Screening Pattern Diagram

Figure 2: Complete tumor clearance in all mice treated with the CCL11-prepared anti-tumor vaccine

1. Verify Consistency: In the development of mRNA vaccines, the strategy of chemokine-linked antigens has been validated with results equivalent to those of DNA vaccines. While enhancing the level of specific T-cell immune response induced by the vaccine, it also improves the anti-tumor immune therapeutic effect of the vaccine, confirming the effectiveness and feasibility of this strategy in mRNA vaccine development.

2. CCL11-Antigen Fusion mRNA Vaccine Shows Great Potential: The strategy of linking antigens through chemokines has shown great potential for CCL11-antigen fusion mRNA vaccines. Compared with the vehicle control group and the antigen control group without linked chemokines, the experimental group exhibited a stronger anti-tumor effect (see Figure 3).

Figure 3: The anti-tumor effect of CCL11-E6E7 fusion mRNA is superior to the control group

3. Self-replicating mRNA (saRNA) vaccines show significant efficacyIn another mRNA vaccine-based study, the research team adopted a strategy of linking chemokines to antigens, connecting CCL11 with the HPV E6E7 antigen to develop a self-replicating saRNA vaccine. Experimental results showed that using only a low dose of 2 ug of saRNA completely eliminated an initial tumor of 100mm³ (see Figure 4). This breakthrough not only validates the high efficiency of saRNA technology but also fully demonstrates the significant potential of the chemokine-linked antigen strategy in cancer immunotherapy.

Figure 4: CCL11-E6E7 Fusion saRNA Achieves 100% Elimination of Large Tumors

In subsequent studies, the article delves into the impact of the CCL11-enhanced nucleic acid vaccine on CD8+ T cells within tumors. The results show a significant increase in the number of specific CD8+ T cells in treated mice.RNA-Seq analysis showed that the CCL11 vaccine promoted immune cell infiltration within the tumor, successfully transforming the tumor microenvironment into an anti-tumor inflammatory environment.This result not only provides important clues for revealing the anti-tumor mechanism of CCL11 but also demonstrates its great therapeutic potential and clinical application prospects (see Figure 5).

Figure 5: Changes in Specific T Cells and Immune Pathways Within Tumors in the CCL11 Vaccine Treatment Group

Studies have shown that stem cell-like memory T cells (Tscm) in lymph nodes possess potent anti-tumor capabilities. The article evaluates the effect of the number of such cells induced by the CCL11 vaccine. The results show that, compared to the control group, the number of Tscm in vaccinated mice significantly increased, which demonstratesCCL11 can promote memory T cell differentiation, demonstrating its potential clinical value.. (See Figure 6)

Figure 6: CCL11-prepared vaccine induces higher-quality specific T cells

Academician Jiang Jiandong said:The development of anti-tumor vaccines requires a systematic analysis of the relationship between tumors and the immune system, aiming for a comprehensive understanding to target effectively. This study evaluated the role of all chemokines in enhancing vaccine-induced immune responses, offering potential adjuvant options for developing vaccines against various diseases such as tumors and viruses. Importantly, our research uncovered the significant role of previously overlooked immune subsets in promoting memory T-cell formation, and the underlying mechanisms warrant further in-depth exploration.

This study not only has significant theoretical implications but also boasts extremely broad application prospects.By improving the immunogenicity of vaccines, we can reduce their dosage, thereby decreasing potential toxicity.Moreover, depending on different types of diseases, we can tailor the most suitable chemokines to develop more precise and effective vaccine products, which can be further integrated with advanced treatment methods such as immune checkpoint inhibitors and CAR-T. This research achievement will provide new perspectives and strategies for the field of cancer treatment, and is expected to bring safer and more effective treatment options to patients.

NEWISH is an innovative drug company focused on the early treatment of tumors and has entered the clinical stage. The company is committed to developing First-in-Class new drugs with complete independent intellectual property rights. This important research achievement not only provides new strategies and directions for the field of tumor nucleic acid vaccine development but also demonstrates NEWISH's scientific research capabilities. With in-depth research into the mechanisms of chemokines, the NEWISH team is confident in designing more efficient and safer tumor nucleic acid vaccines, bringing revolutionary breakthroughs to the field of tumor treatment. In the future, NEWISH will achieve more accomplishments in scientific research and make greater contributions to the cause of human health.

The content of this press release is based on the paper "Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response" published by the NEWISH biological team in the journal Molecular Cancer. This research was supported by projects including the Innovation Project of the Chinese Academy of Medical Sciences (2022-I2M-1-016), the National Natural Science Foundation of China (82151525), and the Beijing Nova Program.

Paper link: https://doi.org/10.1186/s12943-024-01958-4