QichenSheng Bio's Survivin-Targeting mRNA-DC Cancer Vaccine Becomes World's First to Enter Clinical Trials, Marking a Milestone in China's mRNA Therapeutics Advancement
The success of mRNA technology in COVID-19 vaccines is merely the beginning; the era of mRNA cancer vaccines is imminent.
From the first successful extraction of mRNA in 1960 to the successful market launch of mRNA-based COVID-19 vaccines in 2020, six decades of continuous technological refinement have endowed mRNA technology with epoch-making significance. Nevertheless, conquering cancer remains the unwavering mission of mRNA technology.
Recently, in an interview with the BBC, BioNTech founders Uğur Şahin and Özlem Türeci announced that BioNTech had achieved a breakthrough in the field of mRNA cancer vaccines, with expectations for market launch before 2030. Meanwhile, Moderna and Merck jointly announced that the Phase 2b clinical trial of their mRNA vaccine mRNA-4157 in combination with Keytruda for the treatment of melanoma had met its primary endpoint, reducing the risk of recurrence or death by 44%. The global strategic positioning and clear direction for mRNA tumor vaccines have served as a refreshing breeze from late 2022 into 2023, guiding and reinforcing persistence and confidence in R&D and investment within the biopharmaceutical sector.
At the start of the new year, good news emerged from China’s mRNA cancer vaccine R&D sector: “Survivin-Targeted DC Cell Injection,” an mRNA-DC vaccine for the treatment of glioblastoma developed by Qichensheng Biopharma, has officially received clinical trial approval from the National Medical Products Administration (NMPA). It is the first mRNA-DC cancer vaccine approved for clinical trials in China and the world’s first mRNA-DC therapeutic cancer vaccine targeting Survivin to gain such approval.
Survivin, the target of this product and known as the "survival protein," is an anti-apoptotic protein with tumor specificity. It is highly expressed in many types of tumors—including 95% of malignant gliomas, multiple myeloma, medulloblastoma, melanoma, and renal, breast, and ovarian cancers—and is closely associated with tumor cell differentiation, proliferation, invasion, and metastasis. Survivin helps tumor cells resist conventional therapies while remaining unexpressed in normal, differentiated mature tissues, making it an ideal target for cancer therapy. International research on Survivin-targeted cancer treatments has confirmed its efficacy. A Phase IIa clinical trial involving patients with glioma, published in the Journal of Clinical Oncology (Impact Factor: 50.717) on December 15, 2022, demonstrated that 95.2% of patients remained progression-free six months after diagnosis. The SurVaxM vaccine used in the trial stimulates Survivin-specific CD8+ T-cell and antibody responses.
Dendritic cells (DCs) are the most potent antigen-presenting immune cells known in vivo and serve as initiators of adaptive immune responses. They efficiently capture, process, and present antigens, and are the only professional antigen-presenting cells capable of activating naïve T cells. Occupying a central role in the human immune response, DCs are widely utilized in cancer therapy. Recently, researchers from King’s College Hospital London and other institutions reported results from a Phase III non-randomized controlled trial targeting glioma. The study found that treatment with DCVax-L (a dendritic cell vaccine loaded with autologous tumor lysates) significantly extended median overall survival in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) compared to the control group. Notably, this marks the first time in 17 years that such significant results have been achieved in a Phase III trial of systemic therapy for nGBM, and the first time in 27 years that a therapy has demonstrated prolonged survival in rGBM.
Qichensheng Biotechnology’s targeted Survivin dendritic cell (DC) injection involves loading Survivin antigen mRNA onto autologous DCs from patients. Upon reinfusion, it induces various antigen-specific CD4+ and CD8+ T lymphocytes, continuously activating the patient’s immune system. This provides a novel therapeutic approach for postoperative clearance of residual tumor cells in patients with primary glioblastoma, preventing recurrence, extending survival, and achieving long-term anti-tumor effects. DC-based tumor mRNA vaccines represent a highly promising treatment modality for glioblastoma.
Qichensheng Biologics selected Survivin as the target antigen and dendritic cells (DCs) as the delivery vector, while employing its proprietary TriVac antigen modification technology to effectively enhance the presentation of major histocompatibility complex (MHC) class I and II antigens, thereby substantially boosting induced antigen-specific T-cell responses. Preliminary non-clinical studies and data from investigator-initiated exploratory clinical trials have demonstrated that this mRNA-DC vaccine can induce Survivin-specific anti-tumor immune responses, exhibits a favorable safety profile and significant efficacy, and significantly prolongs overall survival in trial patients.
TriVac technology is one of Qichensheng’s core technologies and a globally leading patented platform for functional antigen modification. Its unique advancements enable the delivery of targeted “signals” to antigens through functional modification, thereby efficiently activating three specific effector lymphocytes of the adaptive immune system—B cells, CD4+ T cells, and CD8+ T cells—to significantly enhance antigen-specific immune responses. As a broadly applicable platform technology, TriVac allows for directed functional modification of different tumor-associated antigens (TAAs) tailored to individual patient conditions and clinical strategies, meeting the needs of personalized therapy and expanding its application to the development of mRNA drugs for other diseases.
During the development of the Survivin-targeted dendritic cell (DC) injection, Qichensheng Biotech applied a personalized combination immunotherapy approach, integrating cell therapy and gene therapy to establish a unique clinical treatment strategy.
In early November 2022, a research team comprising Qichensheng Biotechnology, the Department of Clinical Immunology and the Department of Neurosurgery at Xijing Hospital, the National Center for Translational Medicine in Molecular Medicine and the Department of Cell Biology at Air Force Medical University, the Department of Pharmacology and Molecular Sciences at Johns Hopkins University School of Medicine, and the Department of Immunology at Duke University Medical Center, published an online case report on combination immunotherapy for glioblastoma. The report demonstrated that treating a patient with grade IV glioblastoma (GBM) using this mRNA-DC vaccine in combination with anti-PD-1 and Poly I:C resulted in a progression-free survival of over five years, yielding encouraging outcomes. This study represents the first global report of a combination immunotherapy regimen consisting of an mRNA-DC vaccine, anti-PD-1, and Poly I:C achieving the intended goal of “maximizing the likelihood of cure.”
Qichensheng Bio’s mRNA-DC vaccine, “Targeted Survivin Dendritic Cell Injection,” has undergone seven years of research and development, encompassing antigen screening, sequence design, functional modification, dendritic cell (DC) loading, investigator-initiated trial (IIT) clinical validation, chemistry, manufacturing, and controls (CMC) translational studies, pilot-scale optimization, and pharmaceutical research. The project has achieved significant breakthrough innovations in nucleic acid technology, delivery systems, and manufacturing processes. During the Investigational New Drug (IND) application process, exceptionally comprehensive preclinical study results were submitted as technical support. As the first mRNA-based therapeutic cancer vaccine approved for clinical trials in China, it represents a major breakthrough and holds milestone significance for the development of mRNA nucleic acid drugs in the country. In the field of domestic mRNA-encoded DC personalized cancer vaccines, Qichensheng Bio is both a pioneer and a leader in this sector.
Notably, the series of tumor-associated antigens selected for Qichensheng Bio’s mRNA-DC cell-based tumor vaccine are not only targeted at glioma but also extend to multiple other indications, including melanoma, head and neck cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal cancer, and breast cancer. As more clinical trials advance and data are disclosed in the future, the mRNA-DC cell-based tumor vaccine is poised to become another powerful tool in oncology treatment, offering patients safer, more effective, and feasible therapeutic options.
The global biopharmaceutical sector’s strong enthusiasm for mRNA technology, particularly in the field of tumor vaccines, stems from confidence in its substantial clinical and market potential, as well as the revolutionary transformation it brings to cancer therapy. In 2020, Qichensheng Biotech announced that it had secured Pre-A round financing from Sunshine Ronghui Capital. In 2021, the company completed another Pre-A+ round of financing amounting to hundreds of millions of RMB, led by CICC Qide Innovative Biopharmaceutical Venture Investment Fund under CICC Capital, with continued investment from existing shareholder Sunshine Ronghui Capital. These two rounds of funding have effectively accelerated the development of multiple pipeline products at Qichensheng Biotech, including the “Survivin-Targeted Dendritic Cell Injection,” while also driving iterative upgrades of its platform technology and enhancing production capacity, thereby achieving anticipated technical milestones and market targets.
Recently, Qichensheng Biopharma and China Resources Biopharmaceutical signed a strategic cooperation agreement to jointly develop an mRNA vaccine for the treatment of glioblastoma. The partnership aims to further strengthen the iterative optimization and comprehensive upgrading of their technology platforms, enhance empowerment of industrial economic development and global commercial layout, and accelerate the manufacturing translation and clinical application of mRNA therapeutics. By leveraging its proprietary platform technologies, Qichensheng Biopharma is emerging as a notable player in the burgeoning mRNA industry.