Sep 22, 2025

Neoantigens—tumor-specific peptides derived from somatic mutations—represent a cornerstone of personalized cancer immunotherapy due to their absence in normal tissues, minimizing off-target autoimmunity and central tolerance mechanisms. However, their clinical translation has been hindered by suboptimal immunogenicity, inefficient lymph node (LN) trafficking, and limited cross-presentation by antigen-presenting cells (APCs), particularly dendritic cells (DCs). To overcome these barriers, next-generation delivery platforms have emerged, each leveraging distinct biophysical and immunological principles to enhance vaccine efficacy.

Nanoparticles (NPs)-based vaccines

Mechanisms and Advantages

Nanoparticle (NP)-based neoantigen vaccines focus on the co-delivery of tumor-specific antigens and adjuvants to antigen-presenting cells, such as DCs. In this process, cytosolic delivery and cross-presentation of antigens by professional DCs via the major histocompatibility complex class I (MHC-I) antigen-presenting pathway are essential to trigger robust anti-tumor response. Therefore, to fabricate efficient cancer nano-vaccines, it is critical to develop antigen carriers that act as immune adjuvants, and are capable of shuttling antigens directly into the cytosol of APCs^[2].

For cancer immunotherapy, NPs-based vaccine offers distinct advantages.

• Enhanced biodistribution: Efficient accumulation in secondary lymphoid organs, e.g., lymph nodes and penetration of biological barriers.
• Precision co-delivery: Tunable co-encapsulation of antigens and adjuvants for synergistic immune activation.
• Controlled intracellular processing: Improved cytosolic delivery, adjustable antigen release, and promoted cross-presentation in APCs.

Category and characteristic

Challenges and future directions

Despite their potential, NPs face challenges in poor biocompatibility, particle heterogeneity, and inconsistent manufacturing process, thus limiting their application in clinical trials. Moreover, optimizing particle size, charge, and surface chemistry for optimal lymph node drainage and immune activation remains an active area of research. However, protein-caged nanoparticles such as virus-like particles (VLPs) and ferritin family proteins have attracted much attention in drug delivery due to their good biodegradability, highly ordered structure, and simple and repeatable preparation methods.

Liposomes

Mechanisms and Advantages

Figure 1. Liposomes consist of a phospholipid bilayer surrounding an aqueous core, enabling dual loading of hydrophilic antigens in the core and hydrophobic adjuvants or antigens within the bilayer.

Characteristics and advantages

• Compared with neoantigen alone, liposomes protect antigens from degradation, enhance dendritic cell (DC) uptake, and enable adjuvant co-delivery.
• Compared with viral vectors, liposomes offer greater safety (non-replicating), lower immunogenicity, and simpler manufacturing processes.
• Compared with dendritic cell vaccines, liposomes are no need for ex vivo cell processing.

Challenges and future directions

Although liposomes can significantly enhance targeting efficiency and promote cellular uptake, selecting and developing an optimal liposome formulation for neoantigen delivery remains challenging. Moreover, tumor immune escape due to antigenic heterogeneity or downregulation can limit vaccine efficacy. To address this, multivalent liposomes capable of co-delivering 10–20 neoantigens simultaneously offer a promising strategy to broaden T-cell responses and reduce the risk of immune escape. Additionally, stimuli-responsive liposomes (e.g., pH- or redox-sensitive) that enable controlled antigen release in specific microenvironments (such as endosomes or tumor tissues) represent another effective approach to improve vaccine potency

Viral Vectors

Mechanisms and Advantages

Viral vectors are engineered viruses stripped of their pathogenic components but retaining the ability to efficiently deliver genetic material into host cells. In the context of neoantigen-based cancer immunotherapy, viral vectors are used to deliver tumor-specific mutant genes (encoding neoantigens) directly into antigen-presenting cells (APCs), enabling endogenous expression, processing, and presentation on both MHC class I and II—triggering robust CD8⁺ cytotoxic T-cell and CD4⁺ helper T-cell responses.

Characteristics and advantages

• High transduction efficiency: Viruses naturally evolved to enter cells
• Endogenous antigen expression: Allows proper folding, post-translational modifications, and cross-presentation
• Built-in Adjuvanticity: Viral components can activate innate immunity
• Long-lasting cellular responses: Sustained antigen production enhances immune priming
• Multivalent Delivery: Can encode multiple neoantigens in a single vector.

Challenges and future directions

The ability of viral vectors to simultaneously deliver multiple neoantigens is critical for addressing tumor antigen heterogeneity, enabling immune responses against both dominant and subdominant tumor clones and potentially mitigating the risk of immune escape.

However, a major challenge in the clinical application of personalized cancer vaccines is the need for rapid, reliable manufacturing and timely administration of patient-specific formulations—particularly for individuals with advanced-stage disease. Addressing these two challenges—broad antigen coverage and accelerated production timelines—is essential for the successful translation of personalized vaccine therapies.

Partner with Us in Neoantigen Vaccine Innovation

At GenScript, our R&D team engineers neoantigen-delivery systems across all scales—from protein-caged nanoparticles and multivalent liposomes to viral-vector platforms—enabling seamless translation. We partner with academia and industry to resolve every bottleneck, from antigen selection and adjuvant pairing to scalable, GMP-compliant manufacturing.

Explore our neoantigen service—bridging discovery, delivery, and development—for your next-generation cancer vaccine project.

Relevant Resource:

References

• 1. Zheng W , Li S , Shi Z ,et al.Recombinant ferritin-based nanoparticles as neoantigen carriers significantly inhibit tumor growth and metastasis[J].Journal of Nanobiotechnology, 2024, 22(1).DOI:10.1186/s12951-024-02837-2.
• 2. Xu J , Lv J , Zhuang Q ,et al.A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy[J].Nature Nanotechnology, 2020, 15(12):1-10.DOI:10.1038/s41565-020-00781-4.