Special Issue "Cancer Vaccines: Research and Applications"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2018)

Special Issue Editor

Guest Editor
Prof. Dr. Vasso Apostolopoulos

Immunology Program Leader, Institute for Health and Sport, Victoria University, Melbourne VIC 8001, Australia
Website | E-Mail
Interests: immunotherapy, vaccines, antigen delivery, antigen presentation, T cells, MHC-T cell interactions, crystallography

Special Issue Information

Dear Colleagues,

Designing cancer vaccines has been at the forefront of cancer research for over 2 decades. In particular delivery methods used to stimulate effective and long lasting immune responses has been the major focus. This special issue will focus on delivery methods used for cancer vaccines and their outcomes in preclinical studies and clinical trials.

Prof. Dr. Vasso Apostolopoulos
Guest Editor

Manuscript Submission Information

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Keywords

  • Cancer vaccines
  • Delivery methods
  • Dendritic cells
  • Particulate vaccines
  • Adjuvants
  • Peptide based vaccines
  • DNA vaccines
  • T cell responses
  • Clinical outcomes
  • Clinical trials
  • Antigen processing
  • Antigen presentation
  • MHC-T cell interaction

Published Papers (14 papers)

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Research

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Open AccessArticle Identification of Novel HLA Class II-Restricted Neoantigens Derived from Driver Mutations
Cancers 2019, 11(2), 266; https://doi.org/10.3390/cancers11020266
Received: 31 January 2019 / Revised: 18 February 2019 / Accepted: 20 February 2019 / Published: 24 February 2019
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Abstract
Neoantigens derived from tumor-specific genetic mutations might be suitable targets for cancer immunotherapy because of their high immunogenicity. In the current study, we evaluated the immunogenicity of 10 driver mutations that are frequently expressed in various cancers using peripheral blood mononuclear cells from [...] Read more.
Neoantigens derived from tumor-specific genetic mutations might be suitable targets for cancer immunotherapy because of their high immunogenicity. In the current study, we evaluated the immunogenicity of 10 driver mutations that are frequently expressed in various cancers using peripheral blood mononuclear cells from healthy donors (n = 25). Of the 10 synthetic peptides (27-mer) derived from these mutations, the six peptides from KRAS-G12D, KRAS-G12R, KRAS-G13D, NRAS-Q61R, PIK3CA-H1047R, and C-Kit-D816V induced T cell responses, suggesting that frequent driver mutations are not always less immunogenic. In particular, immune responses to PIK3CA-H1047R, C-Kit-D816V, KRAS-G13D, and NRAS-Q61R were observed in more than 10% of the donors. All six peptides induced human leukocyte antigen (HLA) class II-restricted CD4+ T cell responses; notably, PIK3CA-H1047R contained at least two different CD4+ T cell epitopes restricted to different HLA class II alleles. In addition, PIK3CA-H1047R and C-Kit-D816V induced antigen-specific CD8+ T cells as well, indicating that they might contain both HLA class I- and class II-restricted epitopes. Since the identified neoantigens might be shared by patients with various types of cancers and are not easily lost due to immune escape, they have the potential to be promising off-the-shelf cancer immunotherapy targets in patients with the corresponding mutations. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle Activation of CD8+ T Cell Responses after Melanoma Antigen Targeting to CD169+ Antigen Presenting Cells in Mice and Humans
Cancers 2019, 11(2), 183; https://doi.org/10.3390/cancers11020183
Received: 30 November 2018 / Revised: 28 January 2019 / Accepted: 31 January 2019 / Published: 5 February 2019
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Abstract
The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a [...] Read more.
The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs). In human and mouse spleen, we detected CD169+ cells at an equivalent location using immunofluorescence microscopy. Immunization with melanoma antigens conjugated to antibodies (Abs) specific for mouse CD169 efficiently induced gp100 and Trp2-specific T cell responses in mice. In HLA-A2.1 transgenic mice targeting of the human MART-1 peptide to CD169 induced strong MART-1-specific HLA-A2.1-restricted T cell responses. Human gp100 peptide conjugated to Abs specific for human CD169 bound to CD169-expressing monocyte-derived DCs (MoDCs) and resulted in activation of gp100-specific T cells. Together, these data indicate that Ab-mediated antigen targeting to CD169 is a potential strategy for the induction of melanoma-specific T cell responses in mice and in humans. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
Cancers 2019, 11(2), 137; https://doi.org/10.3390/cancers11020137
Received: 3 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 24 January 2019
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Abstract
Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the [...] Read more.
Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. We found that in canine spontaneous gliomas, local injection of a canine-specific, CD200-directed peptide before subcutaneous delivery of an autologous tumor lysate vaccine prolonged survival relative to a historical control treated with autologous tumor lysate alone (median survivals of 12.7 months and 6.36 months, respectively). Antigen-presenting cells and T-lymphocytes primed with this peptide suppressed their expression of the inhibitory CD200 receptor, thereby enhancing their ability to initiate immune reactions in a glioblastoma microenvironment replete with the immunosuppressive CD200 protein. These results support consideration of a CD200 ligand as a novel glioblastoma immunotherapeutic agent. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle A DNA Vaccine Encoding SA-4-1BBL Fused to HPV-16 E7 Antigen Has Prophylactic and Therapeutic Efficacy in a Cervical Cancer Mouse Model
Received: 26 November 2018 / Revised: 3 January 2019 / Accepted: 8 January 2019 / Published: 15 January 2019
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Abstract
The SA-4-1BBL, an oligomeric novel form of the natural ligand for the 4-1BB co-stimulatory receptor of the tumor necrosis factor (TNF) superfamily, as a recombinant protein has potent pleiotropic effects on cells of innate, adaptive, and regulatory immunity with demonstrated therapeutic efficacy in [...] Read more.
The SA-4-1BBL, an oligomeric novel form of the natural ligand for the 4-1BB co-stimulatory receptor of the tumor necrosis factor (TNF) superfamily, as a recombinant protein has potent pleiotropic effects on cells of innate, adaptive, and regulatory immunity with demonstrated therapeutic efficacy in several tumor models. However, the production of soluble form of SA-4-1BBL protein and quality control is time and resource intensive and face various issues pertinent to clinical development of biologics. The present study sought to take advantage of the simplicity and translatability of DNA-based vaccines for the production and delivery of SA-4-1BBL for cancer immune prevention and therapy. A chimeric HPV-16 E7 DNA vaccine (SP-SA-E7-4-1BBL) was constructed that contains the signal peptide (SP) of calreticulin (CRT), streptavidin (SA) domain of SA-4-1BBL, HPV-16 E7 double mutant gene, and the extracellular domain of mouse 4-1BBL. Immunization by gene gun with SP-SA-E7-4-1BBL induced greater prophylactic as well as therapeutic effects in C57BL/6 mice against TC-1 tumor model compared with immunization with E7wt, SP-SA-4-1BBL or reference-positive control CRT-E7wt. The therapeutic efficacy of the DNA vaccine was associated with increased frequency of E7-specific T cells producing interferon (IFN)-γ. Overall, our data suggest that this DNA-based vaccine strategy might represent a translational approach because it provides a simpler and versatile alternative to a subunit vaccine based on SA-4-1BBL and E7 proteins. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle IL-15 and a Two-Step Maturation Process Improve Bone Marrow-Derived Dendritic Cell Cancer Vaccine
Received: 27 November 2018 / Revised: 20 December 2018 / Accepted: 21 December 2018 / Published: 4 January 2019
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Abstract
In the last 20 years, dendritic cells (DCs) have been largely used as a platform for therapeutic vaccination in cancer patients. However, despite its proven safety and ability to induce cancer specific immune responses, the clinical benefits of DC-based immunotherapy are currently very [...] Read more.
In the last 20 years, dendritic cells (DCs) have been largely used as a platform for therapeutic vaccination in cancer patients. However, despite its proven safety and ability to induce cancer specific immune responses, the clinical benefits of DC-based immunotherapy are currently very limited. Thus, novel approaches are still needed to boost its efficacy. Our group recently showed that squaric acid treatment of antigens is an important adjuvant that can increase vaccine-induced downstream immune responses and therapeutic outcomes. Here we further improved this dendritic cell vaccine formulation by developing a new method for differentiating and maturing DCs from their bone marrow precursors. Our data demonstrate that bone marrow-derived DCs differentiated with GM-CSF and IL-15 and matured with a maturation cocktail in two steps present a more mature and immunogenic phenotype, compared to standard DC preparations. Further suppression of the prostaglandin E2 pathway achieved even more immunogenic DC phenotypes. This vaccine was more potent at delaying tumor growth, improved animal survival and induced a more immunogenic and Th1-skewed T cell response in an ovarian cancer mouse model. These promising results support future efforts for the clinical translation of this approach. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
Received: 26 November 2018 / Revised: 21 December 2018 / Accepted: 23 December 2018 / Published: 31 December 2018
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Abstract
Ovarian cancers (OCs) are the most lethal gynaecological malignancy, with high levels of relapse and acquired chemo-resistance. Whilst the tumour–immune nexus controls both cancer progression and regression, the lack of an appropriate system to accurately model tumour stage and immune status has hampered [...] Read more.
Ovarian cancers (OCs) are the most lethal gynaecological malignancy, with high levels of relapse and acquired chemo-resistance. Whilst the tumour–immune nexus controls both cancer progression and regression, the lack of an appropriate system to accurately model tumour stage and immune status has hampered the validation of clinically relevant immunotherapies and therapeutic vaccines to date. To address this need, we stably integrated the near-infrared phytochrome iRFP720 at the ROSA26 genomic locus of ID8 mouse OC cells. Intrabursal ovarian implantation into C57BL/6 mice, followed by regular, non-invasive fluorescence imaging, permitted the direct visualization of tumour mass and distribution over the course of progression. Four distinct phases of tumour growth and dissemination were detectable over time that closely mimicked clinical OC progression. Progression-related changes in immune cells also paralleled typical immune profiles observed in human OCs. Specifically, we observed changes in both the CD8+ T cell effector (Teff):regulatory (Treg) ratio, as well as the dendritic cell (DC)-to-myeloid derived suppressor cell (MDSC) ratio over time across multiple immune cell compartments and in peritoneal ascites. Importantly, iRFP720 expression had no detectible influence over immune profiles. This new model permits non-invasive, longitudinal tumour monitoring whilst preserving host–tumour immune interactions, and allows for the pre-clinical assessment of immune profiles throughout disease progression as well as the direct visualization of therapeutic responses. This simple fluorescence-based approach provides a useful new tool for the validation of novel immuno-therapeutics against OC. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
Cancers 2018, 10(11), 446; https://doi.org/10.3390/cancers10110446
Received: 14 September 2018 / Revised: 9 November 2018 / Accepted: 12 November 2018 / Published: 15 November 2018
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Abstract
Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, [...] Read more.
Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7’ antigen (E7’) as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7’ (ADSC-E7’-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer
Cancers 2018, 10(11), 405; https://doi.org/10.3390/cancers10110405
Received: 16 September 2018 / Revised: 8 October 2018 / Accepted: 26 October 2018 / Published: 28 October 2018
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Abstract
Cancer vaccines based on plasmid DNA represent a good therapeutic perspective, despite their low potency. Animal-derived hyaluronidases (Hyals) are employed in oncological clinical practice. Hyal has been also demonstrated to be a good enhancer of intramuscular Gene Electro-Transfer (GET) efficiency in anti-cancer preclinical [...] Read more.
Cancer vaccines based on plasmid DNA represent a good therapeutic perspective, despite their low potency. Animal-derived hyaluronidases (Hyals) are employed in oncological clinical practice. Hyal has been also demonstrated to be a good enhancer of intramuscular Gene Electro-Transfer (GET) efficiency in anti-cancer preclinical protocols, with increased transfected cells and higher expression of the encoded genes. Nevertheless, the use of animal-derived Hyals results limited respect to their potentialities, since such preparations could be affected by low purity, variable potency and uncertain safety. To improve the delivery of intramuscular GET-based protocols in mouse, we investigated a new recombinant Hyal, the rHyal-sk, to assess in vivo safety and activity of this treatment at cellular and biochemical levels. We evaluated the cellular events and the inflammation chemical mediators involved at different time points after rHyal-sk administration plus GET. Our results demonstrated the in vivo safety and efficacy of rHyal-sk when injected once intramuscularly in association with GET, with no toxicity, good plasmid in-take ability, useful inflammatory response activation, and low immunogenicity. Following these findings, we would recommend the use of the new rHyal-sk for the delivery of DNA-based vaccines and immunotherapy, as well as into clinical practice, for tumor disease treatments. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessArticle Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
Cancers 2018, 10(8), 276; https://doi.org/10.3390/cancers10080276
Received: 29 June 2018 / Revised: 13 August 2018 / Accepted: 14 August 2018 / Published: 20 August 2018
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Abstract
The cancer testis antigen sperm protein 17 (Sp17) is a promising antigenic target in epithelial ovarian cancer (EOC) vaccine development. However, its role in ovarian cancer is unclear. We isolated and expanded Sp17+ and Sp17 clones from the murine EOC cell [...] Read more.
The cancer testis antigen sperm protein 17 (Sp17) is a promising antigenic target in epithelial ovarian cancer (EOC) vaccine development. However, its role in ovarian cancer is unclear. We isolated and expanded Sp17+ and Sp17 clones from the murine EOC cell line ID8, and compared their in-vitro cell growth characteristics and in-vivo tumorigenicity. We also examined the potential co-expression of molecules that may influence cancer cell survival and interaction with immune cells. These include stimulatory and immunosuppressive molecules, such as major histocompatibility class I molecules (MHC I), MHC II, cytotoxic T lymphocyte associated antigen-4 (CTLA-4), CD73, CD39, tumor necrosis factor receptor II (TNFRII), signal transducer and activator of transcription 3 (STAT3) and programmed death-ligand 1 (PD-L1). Whilst the presence of Sp17 was not correlated with the ID8 cell proliferation/growth capacity in vitro, it was critical to enable progressive tumor formation in vivo. Flow cytometry revealed that Sp17+ ID8 cells displayed higher expression of both STAT3 and PD-L1, whilst MHC II expression was lower. Moreover, Sp17high (PD-L1+MHCII) cell populations showed significantly enhanced resistance to Paclitaxel-induced cell death in vitro compared to Sp17low (PD-L1MHCII+) cells, which was associated in turn with increased STAT3 expression. Together, the data support Sp17 as a factor associated with in-vivo tumor progression and chemo-resistance, validating it as a suitable target for vaccine development. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Review

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Open AccessReview Releasing the Immune System Brakes Using siRNAs Enhances Cancer Immunotherapy
Cancers 2019, 11(2), 176; https://doi.org/10.3390/cancers11020176
Received: 6 January 2019 / Revised: 29 January 2019 / Accepted: 31 January 2019 / Published: 3 February 2019
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Abstract
Therapeutic dendritic cell (DC) cancer vaccines rely on the immune system to eradicate tumour cells. Although tumour antigen-specific T cell responses have been observed in most studies, clinical responses are fairly low, arguing for the need to improve the design of DC-based vaccines. [...] Read more.
Therapeutic dendritic cell (DC) cancer vaccines rely on the immune system to eradicate tumour cells. Although tumour antigen-specific T cell responses have been observed in most studies, clinical responses are fairly low, arguing for the need to improve the design of DC-based vaccines. The incorporation of small interfering RNAs (siRNAs) against immunosuppressive factors in the manufacturing process of DCs can turn the vaccine into potent immune stimulators. Additionally, siRNA modification of ex vivo-expanded T cells for adoptive immunotherapy enhanced their killing potency. Most of the siRNA-targeted immune inhibitory factors have been successful in that their blockade produced the strongest cytotoxic T cell responses in preclinical and clinical studies. Cancer patients treated with the siRNA-modified DC vaccines showed promising clinical benefits providing a strong rationale for further development of these immunogenic vaccine formulations. This review covers the progress in combining siRNAs with DC vaccines or T cell therapy to boost anti-tumour immunity. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessReview Anti-Cancer Vaccine for HPV-Associated Neoplasms: Focus on a Therapeutic HPV Vaccine Based on a Novel Tumor Antigen Delivery Method Using Endogenously Engineered Exosomes
Cancers 2019, 11(2), 138; https://doi.org/10.3390/cancers11020138
Received: 29 November 2018 / Revised: 21 January 2019 / Accepted: 22 January 2019 / Published: 24 January 2019
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Abstract
Some human papillomavirus (HPV) genotypes are universally recognized as major etiological agents not only of ano-genital tumors but also of head and neck cancers, which show increasing incidence. The evaluation of current and future therapeutic approaches against HPV-induced tumors is a global health [...] Read more.
Some human papillomavirus (HPV) genotypes are universally recognized as major etiological agents not only of ano-genital tumors but also of head and neck cancers, which show increasing incidence. The evaluation of current and future therapeutic approaches against HPV-induced tumors is a global health priority, despite an effective prophylactic vaccine against 7 of the 12 genotypes involved in the etiology of tumors being currently available. In this review, we present the main anti-HPV therapeutic approaches in clinical experimentation, with a focus on a novel tumor antigen delivery method using engineered exosomes, that we recently developed. Our system allows the induction of an efficient unrestricted cytotoxic T lymphocyte (CTL) immune response against the HPV16-E7 tumor-associated antigen, with the formation of endogenously engineered exosomes, i.e., nanovesicles spontaneously released by all cell types. Immunogenic exosomes are uploaded with HPV16-E7 due to the fusion with a unique exosome-anchoring protein referred to as Nefmut. Intramuscular injection of a DNA vector expressing the fusion protein generates exosomes sufficiently immunogenic to elicit a potent anti-16E7 CTL immune response. The approach is described here and the advantages over other existing methodologies are reported. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessReview Cancer Immunotherapy: Silencing Intracellular Negative Immune Regulators of Dendritic Cells
Cancers 2019, 11(1), 108; https://doi.org/10.3390/cancers11010108
Received: 30 November 2018 / Revised: 9 January 2019 / Accepted: 13 January 2019 / Published: 17 January 2019
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Abstract
Dendritic cells (DCs) are capable of activating adaptive immune responses, or inducing immune suppression or tolerance. In the tumor microenvironment, the function of DCs is polarized into immune suppression that attenuates the effect of T cells, promoting differentiation of regulatory T cells and [...] Read more.
Dendritic cells (DCs) are capable of activating adaptive immune responses, or inducing immune suppression or tolerance. In the tumor microenvironment, the function of DCs is polarized into immune suppression that attenuates the effect of T cells, promoting differentiation of regulatory T cells and supporting tumor progression. Therefore, blocking negative immune regulators in DCs is considered a strategy of cancer immunotherapy. Antibodies can target molecules on the cell surface, but not intracellular molecules of DCs. The delivery of short-hairpin RNAs (shRNA) and small-interfering RNAs (siRNA) should be a strategy to silence specific intracellular targets in DCs. This review provides an overview of the known negative immune regulators of DCs. Moreover, a combination of shRNA/siRNA and DC vaccines, DNA vaccines in animal models, and clinical trials are also discussed. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Open AccessReview Optimising Cancer Vaccine Design in Sarcoma
Received: 21 November 2018 / Revised: 15 December 2018 / Accepted: 18 December 2018 / Published: 20 December 2018
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Abstract
Immunotherapeutics are increasingly recognized as a key tool in the armamentarium against malignancy. The success of immune checkpoint-targeting drugs and adoptive cell therapy has refocused attention on the potential anti-cancer effect of eliciting a tumour-specific immunological response. Sarcomas are a rare and diverse [...] Read more.
Immunotherapeutics are increasingly recognized as a key tool in the armamentarium against malignancy. The success of immune checkpoint-targeting drugs and adoptive cell therapy has refocused attention on the potential anti-cancer effect of eliciting a tumour-specific immunological response. Sarcomas are a rare and diverse group of tumours with a limited prognosis in advanced disease despite systemic therapeutics. Various vaccine strategies including peptide vaccines against cancer testis antigens, dendritic cell vaccines, and viral vectors have been trialled in sarcoma with growing evidence of efficacy. Here, we review the principles of successful vaccine development and how these have been applied thus far to the treatment of sarcoma. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
Open AccessReview Oncolytic Viruses for Canine Cancer Treatment
Cancers 2018, 10(11), 404; https://doi.org/10.3390/cancers10110404
Received: 19 September 2018 / Revised: 16 October 2018 / Accepted: 23 October 2018 / Published: 27 October 2018
Cited by 2 | PDF Full-text (849 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oncolytic virotherapy has been investigated for several decades and is emerging as a plausible biological therapy with several ongoing clinical trials and two viruses are now approved for cancer treatment in humans. The direct cytotoxicity and immune-stimulatory effects make oncolytic viruses an interesting [...] Read more.
Oncolytic virotherapy has been investigated for several decades and is emerging as a plausible biological therapy with several ongoing clinical trials and two viruses are now approved for cancer treatment in humans. The direct cytotoxicity and immune-stimulatory effects make oncolytic viruses an interesting strategy for cancer treatment. In this review, we summarize the results of in vitro and in vivo published studies of oncolytic viruses in different phases of evaluation in dogs, using PubMed and Google scholar as search platforms, without time restrictions (to date). Natural and genetically modified oncolytic viruses were evaluated with some encouraging results. The most studied viruses to date are the reovirus, myxoma virus, and vaccinia, tested mostly in solid tumors such as osteosarcomas, mammary gland tumors, soft tissue sarcomas, and mastocytomas. Although the results are promising, there are issues that need addressing such as ensuring tumor specificity, developing optimal dosing, circumventing preexisting antibodies from previous exposure or the development of antibodies during treatment, and assuring a reasonable safety profile, all of which are required in order to make this approach a successful therapy in dogs. Full article
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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