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The different types of cancer vaccines

The different types of cancer vaccines

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Abstract The recent developments in immuno-oncology have opened an unprecedented avenue for the emergence of vaccine strategies. Therapeutic DNA cancer vaccines are now considered a very promising strategy to activate the immune system against cancer. In the past, several clinical trials using plasmid DNA vaccines demonstrated a good safety profile...

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... to elicit an immune response to arrest the progression of cancer and prevent it from recurring [16]. These include cell-based vaccines, such as dendritic cell vaccines (e.g., Sipuleucel) [17] or whole tumor cells, protein/peptide vaccines [18], viral/bacterial-based vaccines [19,20] and gene-based vaccines, including RNA and DNA vaccines [7,21] (Fig. ...

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... Since they have shown to be well tolerated and safe, their combination with other therapies could become part of the standard of care in many malignancies, with personalized approach, both in vaccine design and in the chosen combination therapy, being crucial for therapeutic success. [28] Nonetheless, one huge hurdle of DNA vaccines manufacturing is their production as plasmids, grown in genetically modified bacteria containing, besides the gene of interest, a bacterial origin of replication and a selective gene, normally encoding for an antibiotic resistance, in order to maintain the persistence of the plasmid in the bacterium. Given the excessive and often inappropriate use of antibiotics, both in human and veterinary medicine, as well as in animal husbandry and agriculture, the last decades have witnessed the spread of these compounds in the environment on a global scale and 5 μg (C). ...
... personalized vaccines and ICIs) in order to prevent the infiltration of immunosuppressive cells and the production of immunosuppressive cytokines has been demonstrated to reduce immunosuppression in the tumor microenvironment, thus improving the modest immunogenicity of DNA cancer vaccines as stand-alone therapy. [28] By demonstrating that DNA amplicons encoding for neoantigens are equally effective as plasmids in antitumoral cotreatment with ICIs (Fig. 5), we here validate the use of amplicon expression vectors as DNA cancer vaccines, as a more cost-and time-effective alternative to conventional plasmids, given their enhanced ability to rapidly manufacture tumor-specific cancer vaccines able to elicit antigenspecific immune responses with increased efficacy and reduced on-target off-tumor effects. ...
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Background DNA-based vaccines represent a simple, safe and promising strategy for harnessing the immune system to fight infectious diseases as well as various forms of cancer and thus are considered an important tool in the cancer immunotherapy toolbox. Nonetheless, the manufacture of plasmid DNA vaccines has several drawbacks, including long lead times and the need to remove impurities from bacterial cultures. Here we report the development of polymerase chain reaction (PCR)-produced amplicon expression vectors as DNA vaccines and their in vivo application to elicit antigen-specific immune responses in animal cancer models. Methods Plasmid DNA and amplicon expression was assessed both in vitro, by Hela cells transfection, and in vivo, by evaluating luciferase expression in wild-type mice through optical imaging. Immunogenicity induced by DNA amplicons was assessed by vaccinating wild-type mice against a tumor-associated antigen, whereas the antitumoral effect of DNA amplicons was evaluated in a murine cancer model in combination with immune-checkpoint inhibitors (ICIs). Results Amplicons encoding tumor-associated-antigens, such as telomerase reverse transcriptase or neoantigens expressed by murine tumor cell lines, were able to elicit antigen-specific immune responses and proved to significantly impact tumor growth when administered in combination with ICIs. Conclusions These results strongly support the further exploration of the use of PCR-based amplicons as an innovative immunotherapeutic approach to cancer treatment.
... Nowadays, a polymerase chain reaction (PCR) approach is being used to amplify the desired DNA sample during vaccine construction [87]. Modern DNA vaccines have increased immunogenicity via codon optimization, the co-administration of cytokines, streamlined plasmids, plasmid-free double-stranded DNA (dsDNA) designs, and vaccine delivery through electroporation [87,90]. A new generation of DNA vaccines was constructed by Vandermeulen et al., who encoded a bio-engineered vesicular stomatitis virus glycoprotein as a carrier of T cell tumor epitopes (plasmid to deliver T cell epitopes, pTOP) to improve the stability of naked IVT mRNA-based vaccines, while also applying many encapsulating agents, such as cationic liposomes and N-[1-(2,3-dioleoloxy)propyl]-N, N,Ntrimethyl ammonium chloride 1(DOTAP), to enhance immune response [88]. ...
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Cancer vaccines have been considered promising therapeutic strategies and are often constructed from whole cells, attenuated pathogens, carbohydrates, peptides, nucleic acids, etc. However, the use of whole organisms or pathogens can elicit unwanted immune responses arising from unforeseen reactions to the vaccine components. On the other hand, synthetic vaccines, which contain antigens that are conjugated, often with carrier proteins, can overcome these issues. Therefore, in this review we have highlighted the synthetic approaches and discussed several bioconjugation strategies for developing antigen-based cancer vaccines. In addition, the major synthetic biology approaches that were used to develop genetically modified cancer vaccines and their progress in clinical research are summarized here. Furthermore, to boost the immune responses of any vaccines, the addition of suitable adjuvants and a proper delivery system are essential. Hence, this review also mentions the synthesis of adjuvants and utilization of biomaterial scaffolds, which may facilitate the design of future cancer vaccines.
... Although tumor antigen-derived peptide immunogens for cancer therapeutic vaccines are traditionally used, there are various limitations, including the manufacturing cost and the need for strong adjuvants to induce anti-tumor immunity (4). Alternative types of cancer vaccines in clinical trials such as DNA vaccines (5), autologous patient-derived immune cell vaccines (6), tumor antigen-expressing recombinant virus vaccines (7), and heterologous whole cell vaccines derived from established human tumor cell lines (8) have been reported. Prior to the widely use of mRNA vaccine for COVID-19, the mRNA-based cancer vaccines have been tested in clinical trials (9) such as personalized RNA mutanome vaccine (10) that is highly effective in inducing anti-tumor immunity. ...
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An mRNA with unmodified nucleosides induces type I interferons (IFN-I) through the stimulation of innate immune sensors. Whether IFN-I induced by mRNA vaccine is crucial for anti-tumor immune response remains to be elucidated. In this study, we investigated the immunogenicity and anti-tumor responses of mRNA encoding tumor antigens with different degrees of N1-methylpseudouridine (m1Ψ) modification in B16 melanoma model. Our results demonstrated that ovalbumin (OVA) encoding mRNA formulated in a lipid nanoparticle (OVA-LNP) induced substantial IFN-I production and the maturation of dendritic cells (DCs) with negative correlation with increasing percentages of m1Ψ modification. In B16-OVA murine melanoma model, unmodified OVA-LNP significantly reduced tumor growth and prolonged survival, compared to OVA-LNP with m1Ψ modification. This robust anti-tumor effect correlated with the increase in intratumoral CD40 ⁺ DCs and the frequency of granzyme B ⁺ /IFN-γ ⁺ /TNF-α ⁺ polyfunctional OVA peptide-specific CD8 ⁺ T cells. Blocking type I IFN receptor completely reversed the anti-tumor immunity of unmodified mRNA-OVA reflected in a significant decrease in OVA-specific IFN-γ secreting T cells and enrichment of PD-1 ⁺ tumor-infiltrating T cells. The robust anti-tumor effect of unmodified OVA-LNP was also observed in the lung metastatic tumor model. Finally, this mRNA vaccine was tested using B16 melanoma neoantigens ( Pbk - Actn4 ) which resulted in delayed tumor growth. Taken together, our findings demonstrated that an unmodified mRNA vaccine induces IFN-I production or the downstream signaling cascades which plays a crucial role in inducing robust anti-tumor T cell response for controlling tumor growth and metastasis.
... Meanwhile, nucleic acid-based vaccines have the potential to offer the combined safety and efficacy of live attenuated and subunit vaccines. While DNA vaccines can induce simultaneous humoral immunity and cellular immune responses, their protection efficiency is typically low, and nucleic acid may integrate into the host genes [5,6]. Alternatively, mRNA vaccines are safer and simpler as they do not pose a risk of nucleic acid Abbreviations: CNE, cationic nanoemulsion; COVID-19, Corona Virus Disease 2019; EGFR, epidermal growth factor receptor; ERD, enhanced respiratory disease; FI-RSV, formalin-inactivated RSV; ICAM1, intercellular adhesion molecule 1; LNP, lipid-based nanoparticles; NRM, non-replicating mRNA; NS, non-structural; pre-F, pre-fusion; RSV, Respiratory syncytial virus; SAM, self-amplifying mRNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SH, small hydrophobic protein; M, matrix; N, nuclear; P, phosphoproteins; G, glycoproteins; F, fusion; BAL, bronchoalveolar lavage; NETs, neutrophil extracellular traps; IL, interleukin; LRTIs, lower respiratory tract infections; RBD, receptor binding domain; FDA, Food and Drug Administration; HIV, human immunodeficiency virus. ...
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Respiratory syncytial virus (RSV) is a single-stranded negative-sense RNA virus that is the primary etiologic pathogen of bronchitis and pneumonia in infants and the elderly. Currently, no preventative vaccine has been approved for RSV infection. However, advances in the characterization, and structural resolution, of the RSV surface fusion glycoprotein have revolutionized RSV vaccine development by providing a new target for preventive interventions. In general, six different approaches have been adopted in the development of preventative RSV therapeutics, namely, particle-based vaccines, vector-based vaccines, live-attenuated or chimeric vaccines, subunit vaccines, mRNA vaccines, and monoclonal antibodies. Among these preventive interventions, MVA-BN-RSV, RSVpreF3, RSVpreF, Ad26. RSV.preF, nirsevimab, clesrovimab and mRNA-1345 is being tested in phase 3 clinical trials, and displays the most promising in infant or elderly populations. Accompanied by the huge success of mRNA vaccines in COVID-19, mRNA vaccines have been rapidly developed, with many having entered clinical studies, in which they have demonstrated encouraging results and acceptable safety profiles. In fact, Moderna has received FDA approval, granting fast-track designation for an investigational single-dose mRNA-1345 vaccine against RSV in adults over 60 years of age. Hence, mRNA vaccines may represent a new, more successful, chapter in the continued battle to develop effective preventative measures against RSV. This review discusses the structure, life cycle, and brief history of RSV, while also presenting the current advancements in RSV preventatives, with a focus on the latest progress in RSV mRNA vaccine development. Finally, future prospects for this field are presented.
... The principal concept of a DNA vaccine for lung cancer is to introduce potential and effective tumor antigens into the host and subsequently activate host immune responses to clear tumor cells (Figure 1). To create a powerful DNA vaccine for lung cancer, the specific tumor-antigen-encoding genes or encoded immunostimulatory molecules are cloned into a eukaryotic expression plasmid [16]. These vaccines can be delivered to the host using various vaccination routes, including intramuscular, intradermal, transcutaneous, and mucosal injections [17]. ...
... For instance, more than five different DNA vaccines are licensed and employed in the veterinary industry, and one of the DNA vaccines (Oncept vaccine) in particular is applied to treat canine melanoma based on a xenogenic antigen [21,111,112]. Many clinical trials have investigated the efficacy and safety of designed DNA vaccines against a majority of tumor models, including breast cancer, cervical cancer, pancreatic cancer, prostate cancer, and lung cancer [16]. However, none of these DNA vaccines have been approved for clinical application in lung cancer patients by the FDA or relevant agencies around the world. ...
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Lung cancer is regarded as the major causes of patient death around the world. Although the novel tumor immunotherapy has made great progress in the past decades, such as utilizing immune checkpoint inhibitors or oncolytic viruses, the overall 5-year survival of patients with lung cancers is still low. Thus, development of effective vaccines to treat lung cancer is urgently required. In this regard, DNA vaccines are now considered as a promising immunotherapy strategy to activate the host immune system against lung cancer. DNA vaccines are able to induce both effective humoral and cellular immune responses, and they possess several potential advantages such as greater stability, higher safety, and being easier to manufacture compared to conventional vaccination. In the present review, we provide a global overview of the mechanism of cancer DNA vaccines and summarize the innovative neoantigens, delivery platforms, and adjuvants in lung cancer that have been investigated or approved. Importantly, we highlight the recent advance of clinical studies in the field of lung cancer DNA vaccine, focusing on their safety and efficacy, which might accelerate the personalized design of DNA vaccine against lung cancer.
... Cancer vaccines are predominantly used to induce specific cellular and humoral immune responses by activating the patient's immune system and using tumor cells or tumor antigens to trigger the proliferation of tumor-specific T cells for tumor clearance. 98,99 They are based on tumor-associated antigens and are chiefly classified as cellular vaccines (tumor and dendritic cell vaccines), genetic vaccines, and peptide vaccines. The key to cancer vaccine development is to identify the optimal vaccination antigen, which is selected from tumor cells and presented via MHC-specific peptides, DNA-encoded proteins, and recombinant viral or bacterial vectors expressed in DSC. 100 GVAX is one of the vaccines developed to treat pancreatic cancer but failed to improve survival in phase IIb/III trials in patients with metastatic PDAC. ...
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The discovery of immune checkpoint inhibitors (ICIs) has ushered a new era for immunotherapy against malignant tumors through the killing effects of cytotoxic T lymphocytes in the tumor microenvironment (TME), resulting in long-lasting tumor suppression and regression. Nevertheless, given that ICIs are highly dependent on T cells in the TME and that most tumors lack T-cell infiltration, promoting the conversion of such immunosuppressive “cold” tumors to “hot” tumors is currently a key challenge in tumor immunotherapy. Herein, we systematically outlined the mechanisms underlying the formation of the immunosuppressive TME in cold tumors, including the role of immunosuppressive cells, impaired antigen presentation, transforming growth factor-β, STAT3 signaling, adenosine, and interferon-γ signaling. Moreover, therapeutic strategies for promoting cold tumors to hot tumors with adequate T-cell infiltration were also discussed. Finally, the prospects of therapeutic tools such as oncolytic viruses, nanoparticles, and photothermal therapy in restoring immune activity in cold tumors were thoroughly reviewed.
... Nonetheless, peptide vaccines were restricted as a result of their inimitable peptide epitopes, low molecular weight, simple degradation, and short half-life [72,73]. Plasmid DNA vaccines represented another attractive approach for personalized vaccination because of fabrication easiness and low cost [74]. The probability of integration between host genome and DNA vaccines was extremely low, even lower than spontaneous mutations [75]. ...
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Immunotherapy treatments harnessing the immune system herald a new era of personalized medicine, offering considerable benefits for cancer patients. Over the past years, tumor neoantigens emerged as a rising star in immunotherapy. Neoantigens are tumor-specific antigens arising from somatic mutations, which are proceeded and presented by the major histocompatibility complex on the cell surface. With the advancement of sequencing technology and bioinformatics engineering, the recognition of neoantigens has accelerated and is expected to be incorporated into the clinical routine. Currently, tumor vaccines against neoantigens mainly encompass peptides, DNA, RNA, and dendritic cells, which are extremely specific to individual patients. Due to the high immunogenicity of neoantigens, tumor vaccines could activate and expand antigen-specific CD4+ and CD8+ T cells to intensify anti-tumor immunity. Herein, we introduce the origin and prediction of neoantigens and compare the advantages and disadvantages of multiple types of neoantigen vaccines. Besides, we review the immunizations and the current clinical research status in neoantigen vaccines, and outline strategies for enhancing the efficacy of neoantigen vaccines. Finally, we present the challenges facing the application of neoantigens.
... DNA vaccines are able to migrate to the nucleus for replication, transcription, and antigen production, and then stimulate the immune system by interacting with antigens produced on the host cell surface and their presentation on MHC class I and class II complexes (8,9). DNA vaccines usually utilize a plasmid produced in Escherichia coli as the expression vector and are delivered by intramuscular injection, which can not only induce humoral immunity but also promote the proliferation and differentiation of T cells, thereby leading to cellular immune response (10). ...
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Cancer represents a serious concern for human life and health. Due to drug resistance and the easy metastasis of tumors, there is urgent need to develop new cancer treatment methods beyond the traditional radiotherapy, chemotherapy, and surgery. Bacterial outer membrane vesicles (OMVs) are a type of double-membrane vesicle secreted by Gram-negative bacteria in the process of growth and life, and play extremely important roles in the survival and invasion of those bacteria. In particular, OMVs contain a large number of immunogenic components associated with their parent bacterium, which can be used as vaccines, adjuvants, and vectors to treat diseases, especially in presenting tumor antigens or targeted therapy with small-molecule drugs. Some OMV-based vaccines are already on the market and have demonstrated good therapeutic effect on the corresponding diseases. OMV-based vaccines for cancer are also being studied, and some are already in clinical trials. This paper reviews bacterial outer membrane vesicles, their interaction with host cells, and their applications in tumor vaccines.
... We identified DNA and adenoviruses as the most promising options. DNA vectors are a versatile vaccine platform that have proven effective in delivering bacterial, viral, and tumor-associated antigens in preclinical studies and in early clinical trials [11,12]. We constructed a DNA vaccine plasmid expressing PSMA and then compared two delivery methods, particle-mediated epidermal delivery (PMED) and intramuscular electroporation, to activate T cells in rhesus macaque monkeys. ...
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The development of therapeutic cancer vaccines remains an active area, although previous approaches have yielded disappointing results. We have built on lessons from previous cancer vaccine approaches and immune checkpoint inhibitor research to develop VBIR, a vaccine-based immunotherapy regimen. Assessment of various technologies led to selection of a heterologous vaccine using chimpanzee adenovirus (AdC68) for priming followed by boosts with electroporation of DNA plasmid to deliver T cell antigens to the immune system. We found that priming with AdC68 rapidly activates and expands antigen-specific T cells and does not encounter pre-existing immunity as occurs with the use of a human adenovirus vaccine. The AdC68 vector does, however, induce new anti-virus immune responses, limiting its use for boosting. To circumvent this, boosting with DNA encoding the same antigens can be done repetitively to augment and maintain vaccine responses. Using mouse and monkey models, we found that the activation of both CD4 and CD8 T cells was amplified by combination with anti-CTLA-4 and anti-PD-1 antibodies. These antibodies were administered subcutaneously to target their distribution to vaccination sites and to reduce systemic exposure which may improve their safety. VBIR can break tolerance and activate T cells recognizing tumor-associated self-antigens. This activation lasts more than a year after completing treatment in monkeys, and inhibits tumor growth to a greater degree than is observed using the individual components in mouse cancer models. These results have encouraged the testing of this combination regimen in cancer patients with the aim of increasing responses beyond current therapies.
... Actually, FixVac (BNT111) is an intravenously injected RNA-LPX vaccine that targets four non-mutated tumor-associated antigens that are commonly found in subjects with melanoma, and is currently in an ongoing clinical trial [96]. In addition to mRNA delivery, pDNA delivery is also attractive as a cancer vaccine [97]. Immune cell activation as well as antigen presentation are required for an efficient cancer immunotherapy. ...
Article
A new era of nanomedicines that involve nucleic acids/gene therapy has been opened after two decades in 21st century and new types of more efficient drug delivery systems (DDS) are highly expected and will include extrahepatic delivery. In this review, we summarize the possibility and expectations for the extrahepatic delivery of small interfering RNA/messenger RNA/plasmid DNA/genome editing to the spleen, lung, tumor, lymph nodes as well as the liver based on our studies as well as reported information. Passive targeting and active targeting are discussed in in vivo delivery and the importance of controlled intracellular trafficking for successful therapeutic results are also discussed. In addition, mitochondrial delivery as a novel strategy for nucleic acids/gene therapy is introduced to expand the therapeutic dimension of nucleic acids/gene therapy in the liver as well as the heart, kidney and brain.