Search Results (45)

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the AI’s impact on LNP engineering through machine learning-driven predictive models, generative adversarial networks (GANs) for novel lipid design, and neural network-enhanced biodistribution prediction. AI reduces the therapeutic development timeline through accelerated virtual screening of millions of lipid combinations, compared to conventional high-throughput screening. Furthermore, AI-optimized LNPs demonstrate improved tumor targeting. GAN-generated lipids show structural novelty while maintaining higher encapsulation efficiency; graph neural networks predict RNA-LNP binding affinity with high accuracy vs. experimental data; digital twins reduce lyophilization optimization from years to months; and federated learning models enable multi-institutional data sharing. We propose a framework to address key technical challenges: training data quality (min. 15,000 lipid structures), model interpretability (SHAP > 0.65), and regulatory compliance (21CFR Part 11). AI integration reduces manufacturing costs and makes personalized cancer vaccine affordable. Future directions need to prioritize quantum machine learning for stability prediction and edge computing for real-time formulation modifications. Full article

RNA-based cancer vaccines have emerged as transformative immunotherapeutic platforms, leveraging advances in mRNA technology and personalized medicine approaches. Recent clinical breakthroughs, particularly the success of mRNA-4157 combined with pembrolizumab in melanoma patients, have demonstrated significant improvements in efficacy, with a 44% reduction in recurrence risk compared to checkpoint inhibitor monotherapy. Breakthrough results from pancreatic cancer vaccines and novel glioblastoma treatments using layered nanoparticle delivery systems mark 2024–2025 as a pivotal period for RNA cancer vaccine development. Current RNA vaccine platforms include conventional mRNA, self-amplifying RNA, trans-amplifying RNA, and emerging circular RNA technologies, with over 120 clinical trials currently underway across various malignancies. Critical advances in delivery optimization include next-generation lipid nanoparticles with tissue-specific targeting and novel nanoengineered systems achieving rapid immune system reprogramming. Manufacturing innovations focus on automated platforms, reducing production timelines from nine weeks to under four weeks for personalized vaccines, while costs remain challenging at over $ 100,000 per patient. Artificial intelligence integration is revolutionizing neoantigen selection through advanced algorithms and CRISPR-enhanced platforms, while regulatory frameworks are evolving with new FDA guidance for therapeutic cancer vaccines. Non-coding RNA applications, including microRNA and long non-coding RNA therapeutics, represent emerging frontiers with potential for enhanced immune modulation. With over 60 candidates in clinical development and the first commercial approvals anticipated by 2029, RNA cancer vaccines are positioned to become cornerstone therapeutics in personalized oncology, offering transformative hope for cancer patients worldwide. Full article

With the successful deployment of several mRNA vaccines against SARS-CoV-2, an mRNA vaccine against RSV (respiratory syncytial virus) and a large pipeline of mRNA products against other infectious diseases, cancers and rare diseases, it is important to examine the whole product lifecycle. mRNA technology enables product design, testing and manufacturing systems to be rapidly developed, but these advantages can be lost if other factors that determine public access are not closely considered. This review analyzes key aspects of the mRNA product lifecycle including candidate design, manufacturing, quality systems and product safety and storage. Regulatory thinking is well advanced in some countries but not others, but more thought on the regulation of mRNA vaccines outside of a pandemic situation as well as mRNA therapeutics including individual neoantigen therapies and rare disease treatments is needed. Consumer acceptance—the “social license to operate” around mRNA products—is critical for their uptake, particularly outside of a pandemic. Full article

Despite advances in vaccination and early detection, the total number of cases and deaths from cervical cancer has risen steadily in recent decades, making it the fourth most common type of cancer in women worldwide. Low-income countries in particular struggle with limited resources and treatment limitations for cervical cancer. Thus, effective medicines that are simple to manufacture are needed. The newly developed dual topoisomerase inhibitor P8-D6, with its outstanding ability to induce apoptosis, could be a promising option. In this study, the efficacy of P8-D6 in combination with radiochemotherapy against cervical carcinoma was investigated in established cell lines and in a translational approach in ex vivo patient cells by measuring the cytotoxicity, cell viability and caspase activity in vitro in 2D and 3D cell cultures. Treatment with P8-D6 resulted in significantly greater cytotoxicity and apoptosis induction compared to standard therapeutic cisplatin in both 2D and 3D cell cultures. Specifically, a considerably stronger anti-proliferative effect was observed. The treatment also led to morphological changes and a loss of membrane integrity in the 3D spheroids. Radiotherapy also benefited greatly from P8-D6 treatment. In fact, P8-D6 was a more potent radiosensitizer than cisplatin. Simple synthesis, favorable physicochemical properties and high potency make P8-D6 a promising cervical cancer drug candidate. Full article

This review evaluates the financial burden of current treatments for triple-negative breast cancer (TNBC) and projects potential financial scenarios to assess the feasibility of introducing a peptide-based neoantigen cancer vaccine (NCV) targeting the disease, using the UK as a healthcare system model. TNBC, the most aggressive breast cancer subtype, is associated with poor prognosis, worsened by the lack of personalised treatment options. Neoantigen cancer vaccine therapies present a personalised alternative with the potential to enhance T-cell responses independently of genetic factors, unlike approved immunotherapies for TNBC. Through a systematic literature review, the underlying science and manufacturing processes of NCVs are explored, the direct medical costs of existing TNBC treatments are enumerated, and two contrasting pricing scenarios for NCV clinical adoption are evaluated. The findings indicate that limited immunogenicity is the main scientific barrier to NCV clinical advancement, alongside production inefficiencies. Financial analysis shows that the UK spends approximately GBP 230 million annually on TNBC treatments, ranging from GBP 2200 to GBP 54,000 per patient. A best-case pricing model involving government-sponsored NCV therapy appears financially viable, while a worst-case, privately funded model exceeds the National Institute for Health and Care Excellence (NICE) cost thresholds. This study concludes that while NCVs show potential clinical benefits for TNBC, uncertainties about their standalone efficacy make their widespread adoption in the UK unlikely without further clinical research. Full article

Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across therapeutic domains, including cancer therapy, neurodegenerative diseases, vaccine development, and regenerative medicine. Innovations in polymer chemistry, surface functionalization, and advanced manufacturing techniques, such as microfluidics and electrospraying, have further enhanced the efficacy and scalability of these systems. This review highlights the key physicochemical properties, preparation strategies, and proven benefits of peptide-loaded PLGA systems, emphasizing their role in sustained drug release, immune activation, and tissue regeneration. Despite remarkable progress, challenges such as production scalability, cost, and regulatory hurdles remain. Full article

Tumors have long posed a significant threat to human life and health, and the messenger ribonucleic acid (mRNA) vaccine is seen as an attractive approach for cancer immunotherapy due to its developmental simplicity, rapid manufacture, and increased immune safety and efficiency. In this review, we have summarized details of the developmental history of mRNA vaccines, discussed the basic molecular structure and the effect on the stable and translation level of mRNA, analyzed the underlying immune efficiency and mechanisms on tumors, and assessed the current status of clinical research. We explored the treatment and application prospects of mRNA vaccines, aiming to provide perspectives on the future of mRNA tumor vaccines for ongoing clinical research. Full article

The rise in biological therapies has revolutionized oncology, with immunotherapy leading the charge through breakthroughs such as CAR-T cell therapy for melanoma and B-ALL. Modified bispecific antibodies and CAR-T cells are being developed to enhance their effectiveness further. However, CAR-T cell therapy currently relies on a costly ex vivo manufacturing process, necessitating alternative strategies to overcome this bottleneck. Targeted in vivo viral transduction offers a promising avenue but remains under-optimized. Additionally, novel approaches are emerging, such as in vivo vaccine boosting of CAR-T cells to strengthen the immune response against tumors, and dendritic cell-based vaccines are under investigation. Beyond CAR-T cells, mRNA therapeutics represent another promising avenue. Targeted delivery of DNA/RNA using lipid nanoparticles (LNPs) shows potential, as LNPs can be directed to T cells. Moreover, CRISPR editing has demonstrated the ability to precisely edit the genome, enhancing the effector function and persistence of synthetic T cells. Enveloped delivery vehicles packaging Cas9 directed to modified T cells offer a virus-free method for safe and effective molecule release. While this platform still relies on ex vivo transduction, using cells from healthy donors or induced pluripotent stem cells can reduce costs, simplify manufacturing, and expand treatment to patients with low-quality T cells. The use of allogeneic CAR-T cells in cancer has gained attraction for its potential to lower costs and broaden accessibility. This review emphasizes critical strategies for improving the selectivity and efficacy of immunotherapies, paving the way for a more targeted and successful fight against cancer. Full article

As one of the most prevalent forms of cancer worldwide, breast cancer has garnered significant attention within the clinical research setting. While traditional treatment employs a multidisciplinary approach including a variety of therapies such as chemotherapy, hormone therapy, and even surgery, researchers have since directed their attention to the budding role of neoantigens. Neoantigens are defined as tumor-specific antigens that result from a multitude of genetic alterations, the most prevalent of which is the single nucleotide variant. As a result of their foreign nature, neoantigens elicit immune responses upon presentation by Major Histocompatibility Complexes I and II followed by recognition by T cell receptors. Previously, researchers have been able to utilize these immunogenic properties and manufacture neoantigen-specific T-cells and neoantigen vaccines. Within the context of breast cancer, biomarkers such as tumor protein 53 (TP53), Survivin, Partner and Localizer of BRCA2 (PALB2), and protein tyrosine phosphatase receptor T (PTPRT) display exceeding potential to serve as neoantigens. However, despite their seemingly limitless potential, neoantigens must overcome various obstacles if they are to be fairly distributed to patients. For instance, a prolonged period between the identification of a neoantigen and the dispersal of treatment poses a serious risk within the context of breast cancer. Regardless of these current obstacles, it appears highly promising that future research into neoantigens will make an everlasting impact on the health outcomes within the realm of breast cancer. The purpose of this literature review is to comprehensively discuss the etiology of various forms of breast cancer and current treatment modalities followed by the significance of neoantigens in cancer therapeutics and their application to breast cancer. Further, we have discussed the limitations, future directions, and the role of transcriptomics in neoantigen identification and personalized medicine. The concepts discussed in the original and review articles were included in this review article. Full article

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others. Full article

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods often utilised for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical, and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products, and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups so that they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission has many potential benefits. These include: reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review. Full article

Biomaterials embody a groundbreaking paradigm shift in the field of drug delivery and human applications. Their versatility and adaptability have not only enriched therapeutic outcomes but also significantly reduced the burden of adverse effects. This work serves as a comprehensive overview of biomaterials, with a particular emphasis on their pivotal role in drug delivery, classifying them in terms of their biobased, biodegradable, and biocompatible nature, and highlighting their characteristics and advantages. The examination also delves into the extensive array of applications for biomaterials in drug delivery, encompassing diverse medical fields such as cancer therapy, cardiovascular diseases, neurological disorders, and vaccination. This work also explores the actual challenges within this domain, including potential toxicity and the complexity of manufacturing processes. These challenges emphasize the necessity for thorough research and the continuous development of regulatory frameworks. The second aim of this review is to navigate through the compelling terrain of recent advances and prospects in biomaterials, envisioning a healthcare landscape where they empower precise, targeted, and personalized drug delivery. The potential for biomaterials to transform healthcare is staggering, as they promise treatments tailored to individual patient needs, offering hope for improved therapeutic efficacy, fewer side effects, and a brighter future for medical practice. Full article

A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumors have been shown both experimentally and clinically to accelerate metastasis to distal organs including the lungs. In this study, we evaluated the efficacy of our engineered nasal nano-vaccine (CpG-NP-Tag) in reducing accelerated lung metastasis resulting from primary tumor resection. Cytosine–phosphate–guanine oligonucleotide [CpG ODN]-conjugated nanoparticle [NP] encapsulating tumor antigen [Tag] (CpG-NP-Tag) was manufactured and tested in vivo using a syngeneic mouse mammary tumor model following intranasal delivery. We found that our nasal nano-vaccine (CpG-NP-Tag), compared to control NPs administered after primary mammary tumor resection, significantly reduced lung metastasis in female BALB/c mice subjected to surgery (surgery mice). An evaluation of vaccine efficacy in both surgery and non-surgery mice revealed that primary tumor resection reduces CD11b⁺ monocyte-derived suppressor-like cell accumulation in the lungs, allowing increased infiltration of vaccine-elicited T cells (IFN-γ CD8⁺ T cells) in the lungs of surgery mice compared to non-surgery mice. These findings suggest that the combination of the target delivery of a nasal vaccine in conjunction with the standard surgery of primary tumors is a plausible adjunctive treatment against the establishment of lung metastasis. Full article

Recent advances and discoveries in the structure and role of mRNA as well as novel lipid-based delivery modalities have enabled the advancement of mRNA therapeutics into the clinical trial space. The manufacturing of these products is relatively simple and eliminates many of the challenges associated with cell culture production of viral delivery systems for gene and cell therapy applications, allowing rapid production of mRNA for personalized treatments, cancer therapies, protein replacement and gene editing. The success of mRNA vaccines during the COVID-19 pandemic highlighted the immense potential of this technology as a vaccination platform, but there are still particular challenges to establish mRNA as a widespread therapeutic tool. Immunostimulatory byproducts can pose a barrier for chronic treatments and different production scales may need to be considered for these applications. Moreover, long-term storage of mRNA products is notoriously difficult. This review provides a detailed overview of the manufacturing steps for mRNA therapeutics, including sequence design, DNA template preparation, mRNA production and formulation, while identifying the challenges remaining in the dose requirements, long-term storage and immunotolerance of the product. Full article

In recent years, with the approval of preventative vaccines for pandemics, lipid nanoparticles have become a prominent RNA delivery vehicle. The lack of long-lasting effects of non-viral vectors is an advantage for infectious disease vaccines. With the introduction of microfluidic processes that facilitate the encapsulation of nucleic acid cargo, lipid nanoparticles are being studied as delivery vehicles for various RNA-based biopharmaceuticals. In particular, using microfluidic chip-based fabrication processes, nucleic acids such as RNA and proteins can be effectively incorporated into lipid nanoparticles and utilized as delivery vehicles for various biopharmaceuticals. Due to the successful development of mRNA therapies, lipid nanoparticles have emerged as a promising approach for the delivery of biopharmaceuticals. Biopharmaceuticals of various types (DNA, mRNA, short RNA, proteins) possess expression mechanisms that are suitable for manufacturing personalized cancer vaccines, while also requiring formulation with lipid nanoparticles. In this review, we describe the basic design of lipid nanoparticles, the types of biopharmaceuticals used as carriers, and the microfluidic processes involved. We then present research cases focusing on lipid-nanoparticle-based immune modulation and discuss the current status of commercially available lipid nanoparticles, as well as future prospects for the development of lipid nanoparticles for immune regulation purposes. Full article