Recent advancements in cancer vaccine developments: novel approaches

Cancer vaccines represent a groundbreaking approach in oncology, aiming to train the immune system to recognize and attack tumor-specific antigens, thereby providing a targeted and potentially long-lasting therapeutic effect. Over the past four decades, extensive research has explored various cancer vaccine strategies, yet their successful clinical translation remains a challenge due to several biological, technical, and logistical barriers. This review delves into the landscape of 360 clinical trials investigating different vaccine modalities, including peptide-based, dendritic cell (DC), RNA, DNA, and viral vector-based vaccines, each with distinct mechanisms, advantages, and limitations. Among these, peptide vaccines have garnered the most attention, comprising 34.2% of trials, particularly for cancers such as melanoma, lung, brain, and breast cancer. While peptide-based vaccines are relatively simple to manufacture and customize, their clinical efficacy is often constrained, necessitating the use of combination therapies to enhance immune response and overcome tumor evasion mechanisms. Similarly, DNA and RNA vaccines have gained momentum with the advent of advanced computational antigen prediction, personalized sequencing, and improved delivery technologies, positioning them as promising candidates for precision oncology. However, the path to clinical success is fraught with hurdles, including immune system suppression by tumors, manufacturing complexities, regulatory challenges, and ethical considerations associated with certain vaccine technologies. Furthermore, despite the theoretical advantages of cancer vaccines, their integration into mainstream oncology is hindered by inconsistent patient responses, the requirement for highly individualized treatment strategies, and the need for robust immune system activation to achieve sustained antitumor effects. This review critically examines these challenges while highlighting recent innovations that have the potential to reshape the field of cancer immunotherapy. As scientific advancements continue to refine antigen selection, vaccine formulation, and delivery methods, cancer vaccines hold the promise of becoming a vital component of multimodal cancer treatment strategies, especially when combined with immune checkpoint inhibitors, chemotherapy, and other emerging therapeutic approaches. By addressing the existing limitations and leveraging cutting-edge technologies, cancer vaccines could ultimately bridge the gap between preclinical potential and clinical efficacy, paving the way for a new era in cancer treatment.

Unlocking Immunity: Innovative prostate cancer vaccine strategies

Cancer vaccine is well recognized as a promising approach for immunotherapy of cancers. Since dendritic cells (DCs) are capable of processing and presenting antigens to initiate the immune response cascade, the development of DC vaccines is considered as a good choice for the treatment of cancer. Herein, a folic acid (FA)-modified liposome was constructed and loaded with chlorin e6 (Ce6) as a DC vaccine (FA-Lipo-Ce6). It was suggested that the loaded Ce6 within FA-Lipo-Ce6 can be activated under laser irradiation. The photodynamic therapy (PDT) of Ce6 was expected to create on-demand reactive oxygen species (ROS) in situ, which causes cell death and trigger the exposure of tumor-associated antigen (TAA). In addition, the produced ROS can mimic the inflammatory responses for the employment of DC for better antigen presentation and immune response. Most importantly, the employment of DC can recognize the exposed TAA to stimulate DC for effective vaccination in situ. Our results demonstrated the powerful capacity of FA-Lipo-Ce6 to induce DC activation, leading to effective suppression of the growth of breast cancers.

Evaluation of quality parameters in thawed dendritic cell vaccine

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.

Melanoma remains one of the deadliest cutaneous malignancies worldwide, and despite advances in systemic therapy, recurrence and treatment resistance remain frequent challenges. Following the success of COVID-19 mRNA vaccines, mRNA-based cancer vaccines targeting melanoma antigens have emerged as a promising therapeutic direction. This review summarizes current evidence on mRNA melanoma vaccines, focusing on two leading delivery platforms: lipid nanoparticles (LNPs) and dendritic cell (DC) vaccines. A comprehensive search of MEDLINE, Embase, and Scopus from 2015 to 2025 identified clinical trials, preclinical studies, and review articles evaluating mRNA vaccine constructs and delivery strategies. Completed clinical studies demonstrate that personalized LNP-formulated mRNA vaccines can enhance neoantigen-specific T-cell responses and improve recurrence-free survival, particularly when combined with immune checkpoint inhibitors. DC-based mRNA vaccines also show potent immunogenicity, with stronger responses observed when DC maturation is optimized. Ongoing trials continue to investigate next-generation LNP formulations, DC priming strategies, and personalized neoantigen approaches. Overall, current evidence indicates that both LNP and DC platforms can augment antitumor immunity by broadening T-cell responses and enhancing checkpoint inhibition. Continued refinement of delivery vehicles, neoantigen selection, and scalable manufacturing processes will be essential to realizing the full clinical potential of mRNA vaccines in melanoma.

The performance and perspectives of dendritic cell vaccines modified by immune checkpoint inhibitors or stimulants

Dendritic cell (DC) vaccines represent a promising advancement in cancer immunotherapy, capitalizing on the unique ability of dendritic cells to initiate and regulate immune responses by presenting antigens to T-cells. These vaccines work by isolating dendritic cells from a patient, loading them with tumor-associated antigens (TAAs), and reinfusing them to stimulate an immune response against cancer cells. The FDA approval of sipuleucel-T (Provenge) for metastatic prostate cancer in 2010 marked a significant milestone in the field, demonstrating the potential for DC vaccines to prolong survival in cancer patients. This review explores the mechanism of action of dendritic cell vaccines, focusing on the process of antigen loading, dendritic cell maturation, and T-cell activation. It also discusses current clinical applications, challenges such as antigen selection, tumor immune evasion, and the high complexity of vaccine production. Future prospects for DC vaccines include personalized cancer vaccines, improved antigen delivery methods, and combination therapies with immune checkpoint inhibitors to enhance effectiveness. Dendritic cell vaccines offer a novel and potentially durable approach to cancer treatment, but further research is needed to optimize their efficacy and broaden their application across various cancer types and other diseases. Keywords: Dendritic cell vaccines, Cancer immunotherapy, Tumor-associated antigens (TAAs), T-cell activation, Combination therapies

BackgroundThe therapeutic efficacy of Dendritic cells (DC) vaccines remains low and there is an unmet need for more effective vaccine design to achieve durable clinical outcomes. Our study analyzed the...

A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high-risk solid tumors using the N-of-1 approach in real-world scenario. A total of 160 evaluable events occurred in 48 patients during the 4-year follow-up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check-point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.

The Covid-19 pandemic has brought about rapid change in medical science. The production of new generation vaccines for this disease has surprised even their most optimistic supporters. Not only have these vaccines proven to be effective, but the importance of this disease and pandemic situation also significantly shortened the long-standing process of validating such products. Vaccination is a type of immunotherapy. Researchers have long been looking at vaccines as a possible treatment for cancer (Geynisman et al., 2014). In the same way that vaccines work against infectious diseases, attempts are being made to develop vaccines to identify specific proteins on cancer cells. This helps the immune system recognize and attack cancer cells. Cancer vaccines may help: I) Prevent the growth of cancer cells (Bialkowski et al., 2016), II) Prevent recurrence of cancer (Stanton and Disis, 2015), III) Destroy cancer cells left over from other treatments. The following types of cancer vaccines are being studied: Antigen Vaccines. These vaccines are made from specific proteins or antigens of cancerous cells. Their purpose is to stimulate the immune system to attack cancer cells (Tagliamonte et al., 2014). Whole-Cell Vaccines. A whole-cell vaccine uses the entire cancer cell, not just a specific molecule (antigen), to generate the vaccine. (Keenan and Jaffee, 2012).Dendritic Cell Vaccines. Dendritic cells help the immune system identify abnormal cells, such as cancerous cells. Dendritic cells are grown with cancer cells in the laboratory to produce the vaccine. The vaccine then stimulates the immune system to attack cancer. (Wang et al., 2014; Mastelic-Gavillet et al., 2019). DNA Vaccines. These vaccines are made from DNA fragments of cancer cells. They can be injected into the body to facilitate immune system cells can better respond and kill cancer cells (Gatti-Mays et al., 2017).Other Types of Cancer Vaccines. such as Anti idiotype vaccines. This vaccine stimulates the body to generate antibodies against cancerous cells. An example of an anti-idiotype antibody is Racotumomab or Vaxira (Cancer, 2016). However, conditions and considerations after Corona does not seem to be the same as before. The current pandemic situation has also led to major changes in the pharmaceutical and Vaccine production process and international protocols. Some of the most critical issues that can accelerate the introduction of cancer vaccines are: 1. Typical drug and vaccine development timeline. A typical vaccine needs 5 to 10 years and sometimes longer to design secure funding, and get approval (Figure 1). Less than 10 percent of new drugs, which are entered in the different phases of clinical trials, are advanced to approval by the Food and Drug Administration (FDA)(Cancer, 2020a). However, now the situation is not normal. Dozens of Covid 19 vaccines are starting clinical trials. Some of them use RNA and DNA technology, which delivers the body with missions to produce its antibodies against the virus. There are already at least 254 therapies and 95 vaccines related to Covid-19 being explored. However, it seems that the experiences gained in this pandemic, and advances in technology, may be effective in shortening the production path of other vaccines and drugs and the process of its approval at the national and international levels in the future. In Figure 2, the time course of production of conventional vaccines in comparison with Covid 19 vaccines (Cancer, 2020b) is shown.2. The introduction of messenger RNA (mRNA) technology into the field of prevention and treatment. Over the past decades, this technology has been considered an excellent alternative to conventional vaccination methods. Proper potency and low side effects, the possibility of fast production and relatively low production cost are its advantages. However, until recently, the instability of this molecule has been a major problem in its application. This research was started many years ago by two companies that played a significant role in developing the first Covid vaccines, so BioNTech and Moderna were able to quickly transfer their experience in the field of Covid vaccine development (Pardi et al., 2018; Moderna, 2020). Figure 3 shows how mRNA vaccines work. Bout Pfizer – BioNTech and Moderna mRNA vaccines were more than 90 % effective in preclinical stages. Millions of doses of these two vaccines are currently being injected into eligible individuals worldwide. 3. Considering the use of artificial intelligence in assessing the effectiveness of vaccines. There are always doubts about the effectiveness of the new drug in treating the disease. Once the vaccine is widely available, we will know more about its effectiveness versus it works under carefully controlled scientific testing conditions. Vaccines will continue to be monitored after use. The data collected helps professionals understand how they work in different groups of people (depending on factors such as age, ethnicity, and people with different health conditions) and also the length of protection provided by the vaccine. Artificial intelligence (AI) is an emerging field, which reaches everywhere and not only as a beneficial industrial tool but also as a practical tool in medical science and plays a crucial role in developing the computation vision, risk assessment, diagnostic, prognostic, etc. models in the field of medicine (Amisha et al., 2019). According to the wide range of AI applications in the analysis of different types of data, it can be used in vaccine production, safety assessments, clinical and preclinical studies and Covid 19 vaccines adverse reactions (CDC, 2019). Indeed, most cancer vaccines are therapeutic, rather than prophylactic, and seek to stimulate cell-mediated responses, such as those from CTLs, capable of clearing or reducing tumor burden. There are currently FDA-approved products for helping cancer treatment such as BREYANZI, TECARTUS and YESCARTA for lymphoma, IMLYGIC for melanoma, KYMRIAH for acute lymphoblastic leukemia, and PROVENGE for prostate cancer. Over the past decade, most of BioNTech's activities have been in the field of cancer vaccine design and production for melanoma (two clinical trials), breast cancer (one clinical trial), and the rest concerning viral and veterinary vaccines (two clinical trials). Also Maderno company has been working on Individualized cancer vaccines (one clinical trials), and vaccines for viral infections such as Zika and Influenza and veterinary vaccines (several clinical trials) (Pardi et al., 2018). Therefore, it can be said, mRNA technology that has been the subject of much research into the treatment of cancer has been shifted and rapidly used to produce and use the Covid 19 vaccine. The current pandemic situation has necessitated the acceleration of Covid 19 vaccines and drugs and national and international protocols for their approval. If the currently produced vaccines can continue to be as successful as the preclinical and early phase studies, these changes and evolution have raised hopes for accelerating the use of these technologies and mechanisms in the field of cancer and other diseases vaccines, including HIV and influenza.

Dendritic cell (DC) vaccines have proven to be a valuable tool in cancer immune therapy. With several DC vaccines being currently tested in clinical trials, knowledge about their therapeutic value has been significantly increased in the past decade. Despite their established safety, it has become clear that objective clinical responses are not yet robust enough, requiring further optimization. Improvements of this advanced therapy medicinal product encompass, among others, regulating their immune stimulating capacity by in situ gene engineering, in addition to their implementation in combination therapy regimens. Previously, we have reported on a superior monocyte-derived DC preparation, including interleukin-15, pro-inflammatory cytokines and immunological danger signals in the culture process. These so-called IL-15 DCs have already proven to exhibit several favorable properties as cancer vaccine. Evolving research into mechanisms that could further modulate the immune response towards cancer, points to programmed death-1 as an important player that dampens anti-tumor immunity. Aiming at leveraging the immunogenicity of DC vaccines, we hypothesized that additional implementation of the inhibitory immune checkpoint molecules programmed death-ligand (PD-L)1 and PD-L2 in IL-15 DC vaccines would exhibit superior stimulatory potential. In this paper, we successfully implemented PD-L silencing at the monocyte stage in the 3-day IL-15 DC culture protocol resulting in substantial downregulation of both PD-L1 and PD-L2 to levels below 30%. Additionally, we validated that these DCs retain their specific characteristics, both at the level of phenotype and interferon gamma secretion. Evaluating their functional characteristics, we demonstrate that PD-L silencing does not affect the capacity to induce allogeneic proliferation. Ultimately designed to induce a durable tumor antigen-specific immune response, PD-L silenced IL-15 DCs were capable of surpassing PD-1-mediated inhibition by antigen-specific T cells. Further corroborating the superior potency of short-term IL-15 DCs, the combination of immune stimulatory components during DC differentiation and maturation with in situ checkpoint inhibition supports further clinical translation.

Dendritic cell vaccine therapy for colorectal cancer

Tumor vaccines for hepatocellular carcinoma (HCC) is an area of intense interest. Tremendous clinical trials have been conducted globally, but the efficacy and security of tumor vaccines are elusive. The aim of our study was to evaluate the efficacy and security of tumor vaccines. All relevant studies were identified in PubMed, EMBASE, Web of science and Cochrane Library databases. Objective response rate (ORR), median overall survival (OS), or median progression-free survival (PFS) and 95% CI were meta-analyzed based on the random-effects model. The individual-level data of OS, PFS were pooled by conducting survival analysis. All observed adverse events were collected. 31 studies containing 35 eligible cohorts with 932 HCC patients were included. The pooled ORR were 7% (95% CI 3-14%), while ORR of dendritic cell (DC) vaccine (19%, 95% CI 11-29%) were highly significant than ORR of peptide vaccine (1%, 95% CI 0-5%). The pooled median OS and PFS were 13.67months (95% CI 8.20-22.80) and 6.19months (95% CI 2.97-12.91), respectively. The pooled median OS (DC vaccine: median OS = 21.77months, 95% CI 18.33-25.86; Peptide vaccine: median OS = 10.08months, 95% CI 5.23-19.44) and PFS (DC vaccine: median PFS = 11.01months, 95% CI 5.25-23.09; Peptide vaccine: median PFS = 1.97months, 95% CI 1.53-2.54) of DC vaccine were also longer than that of peptide vaccine. HBV-related HCC may acquire more benefits from tumor vaccines than HCV-related HCC. In almost all studies, the observed toxicities were moderate even tiny. Tumor vaccines for HCC, especially DC vaccine, are safe and worth exploring. More high-quality prospective studies are warranted.

Dendritic cell (DC) vaccine has been demonstrated to induce antitumor immunity in animal models. It has been shown that the efficiency of antitumor immunity by DC vaccine is closely correlated with DC maturation status. The mature human DCs generated from peripheral blood mononuclear cells (PBMCs) in the presence of granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-4, and tumor necrosis factor (TNF)-alpha have widely contributed to their growing use in cancer vaccination trials. Although the objective clinical immune responses have been observed, the treatment results have proved to be somewhat disappointing. One question of whether these ex vivo-generated mature DCs can maintain their maturation status in vivo after DC vaccination is unclear. In this study, we investigated the influence of different culture media (RPMI 1640/10% fetal calf serum [FCS] versus serum-free AIM-V medium) on DC maturation and the change of maturation status of these ex vivo generated mature DCs during further culturing in medium without inflammatory cytokine TNF-alpha. We previously constructed a recombinant adenovirus AdV-TNF-alpha expressing the transgene human TNF-alpha. We transfected human DCs with AdV-TNF-alpha at multiplicity of infection of 100, resulting in engineered DCs secreting TNF-alpha (4.6 ng/mL/10(6) cells/24 hours). We also conducted kinetic studies to compare the maturation status and the T-cell stimulation capacity by ex vivo-generated mature DCs and TNF-alpha- transgene-engineered DCs during further culturing in medium without TNF-alpha. Our data show that mature DCs can be generated from PBMCs in both Dulbecco's modified Eagle's medium plus 10% FCS and serum-free AIM-V medium containing GM-CSF (100 ng/mL), IL-4 (100 ng/mL), and TNF-alpha (10 ng/mL). However, these mature DCs gradually lost their maturity and became immature ones when culturing in medium in the absence of TNF-alpha. On the contrary, the human DCs engineered to express TNF-alpha can (i) stably maintain their cellular maturation and (ii) efficiently stimulate T-cell proliferation even during culturing ex vivo in medium without TNF-alpha stimulation. Therefore, DCs engineered to express TNF-alpha may also maintain their maturation status and induce more efficient antitumor immune responses when applied in vivo for vaccination. Thus, our results may be important in designing DC-based cancer vaccines in the future.