Search Results (182)

Colorectal cancer (CRC) remains one of the most lethal malignancies worldwide, with high recurrence rates and limited curative options in metastatic settings. Cancer vaccines represent an emerging immunotherapeutic approach that aims to stimulate robust, tumor-specific immune responses. This review summarizes the current state of CRC vaccine development, including tumor cell-based, dendritic cell-based, peptide-based, nucleic acid-based (DNA and mRNA), and virus-based platforms. We highlight findings from key clinical trials that demonstrate immunogenicity, safety, and preliminary efficacy, with particular attention to combinations with chemotherapy and immune checkpoint inhibitors. Furthermore, we explore critical challenges such as tumor heterogeneity, immunosuppressive tumor microenvironments, and the logistical complexity; in this context, we particularly focus on the current development of personalized cancer vaccines, exploring the newly identified encouraging epitopes and their safety and efficacy in recent trials. The integration of cancer vaccines with in silico modeling, advanced delivery systems such as nanoparticles or AI-guided designs, and microbiome modulation represents a promising avenue for enhancing their clinical utility. Overall, therapeutic and prophylactic cancer vaccines may soon contribute meaningfully to the comprehensive management of CRC, especially in settings of minimal residual disease or early recurrence. Full article

Background/Objectives: Leukemia is associated with high recurrence rates and cancer vaccines are emerging as a promising immunotherapy against the disease. Here, we investigate the mechanism of action by which a personalized vaccine made from leukemia cells infected with an oncolytic virus (ICV) induces anti-tumor immunity. Methods: Using the L1210 murine model, leukemia cells were infected and irradiated to create the ICV. The CRISPR-Cas9 system was used to engineer knockout cells to test in treatment efficacy studies. Results: We found that pro-inflammatory interferons (IFNs) that are produced by infected vaccine cells induce the immunoproteasome (ImP), a specialized proteasome subtype that is found in immune cells. Interestingly, we show that while a vaccine using the oncolytic vesicular stomatitis virus (oVSV) completely protects against tumor challenge, the wild-type (wt) virus, which does not induce the ImP, is not as effective. To delineate the contribution of the ImP for vaccine efficacy, we generated ImP-knockout cell lines and found no differences in treatment efficacy compared to wild-type cells. Furthermore, an ICV using another murine leukemia model that expresses the ImP only when infected by an IFN gamma-encoding variant of the virus demonstrated similar efficacy as the parental virus. Conclusions: Taken together, our data show that ImP expression by vaccine cells was not required for the efficacy of leukemia ICVs. Full article

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

Primary and secondary immunodeficiencies comprise a wide array of illnesses marked by immune system abnormalities, resulting in heightened vulnerability to infections, autoimmunity, and cancers. Notwithstanding progress in diagnostic instruments and an enhanced comprehension of the underlying pathophysiology, delayed diagnosis and underreporting persist as considerable obstacles. The implementation of artificial intelligence into clinical practice has surfaced as a viable method to enhance early detection, risk assessment, and management of immunodeficiencies. Recent advancements illustrate how artificial intelligence-driven models, such as predictive algorithms, electronic phenotyping, and automated flow cytometry analysis, might enable early diagnosis, minimize diagnostic delays, and enhance personalized treatment methods. Furthermore, artificial intelligence-driven immunopeptidomics and phenotypic categorization are enhancing vaccine development and biomarker identification. Successful implementation necessitates overcoming problems associated with data standardization, model validation, and ethical issues. Future advancements will necessitate a multidisciplinary partnership among physicians, data scientists, and governments to effectively use the revolutionary capabilities of artificial intelligence, therefore ushering in an age of precision medicine in immunodeficiencies. Full article

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC. Full article

Cutaneous melanoma is an aggressive cancer with an increasing incidence worldwide, highlighting the need for research into its pathogenesis. The tumor microenvironment (TME) plays a critical role in melanoma progression and consists of cellular components and an extracellular matrix (ECM) rich in cytokines and signaling molecules. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs), which remodel the ECM and modulate immune responses. Among immune cells, tumor-associated macrophages (TAMs) predominate, and their polarization toward the M2 phenotype supports tumor progression. Tumor-infiltrating lymphocytes (TILs) have diverse functions, including cytotoxic T-cells, helper T-cells that modulate immune response, B-cells forming tertiary lymphoid structures (TLS), and regulatory T-cells with immunosuppressive properties. Dendritic cells (DCs) also play a complex role in the TME. A notable subpopulation are mature regulatory dendritic cells (mregDCs), which contribute to immune evasion. All of these TME components may drive tumorigenesis. Advancements in melanoma treatment—including immunotherapy and targeted therapies—have significantly improved outcomes in advanced-stage disease. In parallel, emerging approaches targeting the tumor microenvironment and gut microbiome, as well as personalized strategies such as neoantigen vaccines and cell-based therapies, are under active investigation and may further enhance therapeutic efficacy in the near future. Full article

Immuno-oncology has rapidly evolved into a cornerstone of modern cancer therapy, offering promising avenues for durable responses and personalized treatment strategies. This narrative review provides a thorough overview of the mechanisms underlying tumor–immune system interactions and the therapeutic innovations emerging from this knowledge. Central to this discussion is the tumor microenvironment (TME), a complex ecosystem of immune and stromal cells that supports tumor growth and shapes therapeutic outcomes. Key cellular and molecular factors within the TME are examined, along with diverse immune escape strategies. We further analyze the landscape of immunotherapeutic approaches, including immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies such as CAR-T cells, and cytokine-based interventions. This review also addresses the increasing importance of predictive biomarkers in immuno-oncology, particularly in patient stratification, monitoring resistance, and managing immunotherapy-related toxicity. Finally, we explore the emerging role of the microbiome as a modulator of immunotherapy efficacy, shedding light on host–microbe–immune interactions that may influence clinical outcomes. By integrating current biological insights with therapeutic innovation, this review outlines the challenges and opportunities ahead in immuno-oncology and emphasizes the need for translational research and cross-disciplinary collaboration to optimize cancer immunotherapy in the era of precision medicine. Full article

Therapeutic cancer vaccines are a new growth point of biomedicine with broad industrial prospects in the post-COVID-19 era. Many large international pharmaceutical companies and emerging biotechnology companies are deploying different tumor therapeutic cancer vaccine projects, focusing on promoting their clinical transformation, and the vaccine industry has strong momentum for development. Such vaccines are also the core engine and pilot site for the development of new vaccine targets, new vectors, new adjuvants, and new technologies, which play a key role in promoting the innovation and development of vaccines. Various therapeutic cancer vaccines, such as viral vector vaccines, bacterial vector vaccines, cell vector vaccines, peptide vaccines, and nucleic acid vaccines, have all been applied in clinical research. With the continuous development of technology, therapeutic cancer vaccines are evolving towards the trends of precise antigens, efficient carriers, diversified adjuvants, and combined applications. For instance, the rapidly advancing mRNA-4157 vaccine is a typical representative that combines personalized antigens with efficient delivery vectors (lipid nanoparticles, LNPs), and it also shows synergistic advantages in melanoma patients treated in combination with immune checkpoint inhibitors. In this article, we will systematically discuss the current research and development status and clinical research progress of various therapeutic cancer vaccines. Full article

Precision prevention strategies for cervical cancer that integrate genetic biomarkers provide opportunities for personalized risk assessment and optimized preventive measures. An HPV infection–Precancerous–Cancer risk assessment model incorporating genetic polymorphisms and DNA methylation was developed to better understand the regression and progression of cervical lesions by HPV infection status. Utilizing a virtual cohort of 300,000 Taiwanese women aged 30 years and older, our model simulated the natural history of cervical cancer, capturing transitions from a healthy state through precancerous lesions (LSILs and HSILs) to invasive carcinoma and incorporating the possibility of regression between states. Genetic and epigenetic markers significantly influenced disease transitions, demonstrating heterogeneous risks among women with distinct molecular biomarker profiles. Guided by these individual risk profiles, tailored preventive strategies including varying intervals for Pap smear screening, HPV DNA testing, and HPV vaccination showed improved efficiency and effectiveness in reducing cervical cancer incidence compared to uniform approaches. The proposed dynamic transition model of cervical neoplasms incorporating genetic biomarkers can facilitate the development of an individualized risk-based approach for guiding precision prevention towards the goal of cervical cancer elimination. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Background/Objectives: To summarize the relevant trials relating to novel strategies and therapeutic advances in the treatment of bladder cancer. Methods: A comprehensive review of the literature and recent/ongoing clinical trials was conducted, focusing on novel treatments and strategies for bladder cancer. Trials started or published as of 2020 were included. Results: The standard of care for MIBC remains neoadjuvant chemotherapy with perioperative immunotherapy in the cisplatin-eligible population, while guidelines do not exist for cisplatin-ineligible patients. Strategies under investigation include combinations of chemotherapy, immunotherapy, radiation, and/or novel therapies, such as ADCs, targeted agents, intravesical treatments, and personalized vaccines. Bladder-sparing approaches using these novel therapies are also being studied. In the advanced/metastatic setting, enfortumab vedotin plus pembrolizumab has supplanted platinum-based chemotherapy as the first-line treatment option. For those with contraindications, or who progress, strategies under investigation include newer immunotherapies and ADCs, novel small molecule inhibitors, and cellular therapies. Conclusions: The treatment landscape for bladder cancer has changed drastically within the last few years. Ongoing trials hope to build on this success by investigating bladder-sparing strategies for MIBC and novel systemic therapies in advanced patients. Full article

Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer vaccines has emerged as a potential strategy to augment antitumor immune responses. Results: This review compares two promising personalized therapeutic cancer vaccine trials in advanced melanoma: Elios Therapeutics’ Tumor Lysate (TL) vaccine and Moderna’s mRNA-4157 vaccine. The TL vaccine, which utilizes yeast cell wall particles (YCWPs) loaded with autologous tumor lysate, and the mRNA-4157 vaccine, which encodes up to 34 patient-specific neoantigens, both aim to stimulate robust tumor-specific immune responses. Both trials were phase 2b randomized studies, with Elios Therapeutics’ trial employing a double-blind, placebo-controlled design, while Moderna’s was open-label. Both trials had roughly equivalent sample sizes (n = 187 and n = 157, respectively) with similar demographics and disease characteristics. The TL trial reported improvements in disease-free survival (DFS) with a hazard ratio (HR) of 0.52 (p < 0.01) over 36 months, whereas the mRNA-4157 trial demonstrated improvements in recurrence-free survival (RFS) with an HR of 0.56 (p = 0.053) over 18 months. The TL vaccine exhibited lower rates of related grade 3 adverse events (<1%) compared to the mRNA vaccine (12%). Key differences between the two trials include the use of CPIs, with 100% of patients in the mRNA trial receiving pembrolizumab versus 37% of the patients in the TL trial receiving either an anti-PD-1 or anti-CTLA-4. The production processes also varied significantly, with the mRNA vaccine requiring individualized sequencing and a 9-week production time, while the TL vaccine utilized tumor lysate with a 1–3-day production time. Conclusions: While both vaccines demonstrated promising efficacy, future phase 3 trials are needed to further evaluate their potential as adjuvant therapies for melanoma. This review highlights the comparative strengths and limitations of these vaccine platforms, providing insight into the evolving landscape of adjuvant cancer vaccines. Full article

The incidence of melanoma is increasing globally, even in the wake of increased risk factor awareness and a growing body of advanced therapeutic options. It is apparent that the treatment of melanoma will remain a topic of worry in areas of the world under high ultraviolet exposure and areas that harbor individuals with fair skin phenotypes. In the wake of such concern, the potential of immunotherapy and various targeted therapeutics to treat late-stage melanoma is increasing. In addition to the growing arsenal of PD-1 and PD-L1 immune checkpoint inhibitors, other targeted therapies are being developed and tested to treat melanoma. BRAF/MEK inhibitors target a key proliferative pathway in melanoma, offering clinical benefit but limited durability. Next-generation agents and triplet therapy with immunotherapy aim to improve outcomes. Androgen receptor signaling may also modulate responses to both targeted and immune-based treatments. Bispecific T cell engagers assist with guiding the body’s own T cells to tumors where they release toxins that kill the tumor cell. Personalized neoantigen vaccines target tumor-specific antigens by sequencing a patient’s cancerous cells to create tailored vaccines that elicit a strong and specific immune response. Tumor-infiltrating lymphocytes are autologous lymphocytes reinfused back into the host that are showing efficacy in the treatment of advanced melanoma. Together, these therapies are advancing the arsenal of chemotherapeutic options that can be used to inhibit the progression of melanoma. 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

Background/Objectives: Since their approval in early 2020, mRNA vaccines have gained significant attention since the COVID-19 pandemic as a potential therapeutic approach to tackle several infectious diseases. This article aims to review the current state of mRNA vaccine technology and its use against other diseases. Methods: To obtain accurate and reliable data, we carefully searched the clinicaltrial.gov and individual companies’ websites for current ongoing clinical trials reports. Also, we accessed different NCBI databases for recent articles or reports of clinical trials, innovative design of mRNA vaccines, and reviews. Results: Significant progress has been made in the design and improvement of mRNA vaccine technology. Currently, there are hundreds of ongoing clinical trials on mRNA vaccines against different cancer types, infectious diseases, and genetic and rare diseases, which showcase the advancement in this technology and their potential therapeutic advantages over traditional vaccine platforms. Finally, we predict what could be a potential future direction in designing more effective mRNA vaccines, particularly against cancer. Conclusions: The results of many of the ongoing clinical trials have shown significant positive outcomes, with many of the trials already at Phase III. Despite this outlook, however, some have been terminated or withdrawn for several reasons, some of which are not made available. This means that despite the advancement, there is a need for more research and critical evaluation of each innovation to better understand their immunological benefits and long-term effects. Full article