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Vaccines, Volume 3, Issue 3 (September 2015) – 15 articles , Pages 490-802

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Open AccessReview
Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity
Vaccines 2015, 3(3), 771-802; https://doi.org/10.3390/vaccines3030771 - 17 Sep 2015
Cited by 8 | Viewed by 3055
Abstract
Transcription is a dynamic process influenced by the cellular environment: healthy, transformed, and otherwise. Genome-wide mRNA expression profiles reflect the collective impact of pathways modulating cell function under different conditions. In this review we focus on the transcriptional pathways that control tumor infiltrating [...] Read more.
Transcription is a dynamic process influenced by the cellular environment: healthy, transformed, and otherwise. Genome-wide mRNA expression profiles reflect the collective impact of pathways modulating cell function under different conditions. In this review we focus on the transcriptional pathways that control tumor infiltrating CD8+ T cell (TIL) function. Simultaneous restraint of overlapping inhibitory pathways may confer TIL resistance to multiple mechanisms of suppression traditionally referred to as exhaustion, tolerance, or anergy. Although decades of work have laid a solid foundation of altered transcriptional networks underlying various subsets of hypofunctional or “dysfunctional” CD8+ T cells, an understanding of the relevance in TIL has just begun. With recent technological advances, it is now feasible to further elucidate and utilize these pathways in immunotherapy platforms that seek to increase TIL function. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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Open AccessArticle
New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates
Vaccines 2015, 3(3), 751-770; https://doi.org/10.3390/vaccines3030751 - 14 Sep 2015
Cited by 21 | Viewed by 2963
Abstract
Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using [...] Read more.
Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN), were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA) or pertussis toxin (PT) deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE) cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells. Full article
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Open AccessArticle
Chitosan-Poly (I:C)-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines
Vaccines 2015, 3(3), 730-750; https://doi.org/10.3390/vaccines3030730 - 11 Sep 2015
Cited by 8 | Viewed by 3440
Abstract
The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells [...] Read more.
The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C) (pIC) and a T-Helper peptide (PADRE), integrated into a chitosan (CS) based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa) derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm), a high positive surface charge (>40 mV) and high pIC association efficiency (>96%). They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed) on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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Open AccessReview
The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity
Vaccines 2015, 3(3), 703-729; https://doi.org/10.3390/vaccines3030703 - 10 Sep 2015
Cited by 90 | Viewed by 4992
Abstract
Indoleamine 2, 3-dioxygenase (IDO) is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called “kynurenines” [...] Read more.
Indoleamine 2, 3-dioxygenase (IDO) is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called “kynurenines” that are known to exert important immuno-regulatory functions. Because tryptophan must be supplied in the diet, regulation of tryptophan catabolism may exert profound effects by activating or inhibiting metabolism and immune responses. Important for survival, the regulation of IDO biosynthesis and its activity in cells of the immune system can critically alter their responses to immunological insults, such as infection, autoimmunity and cancer. In this review, we assess how IDO-mediated catabolism of tryptophan can modulate the immune system to arrest inflammation, suppress immunity to cancer and inhibit allergy, autoimmunity and the rejection of transplanted tissues. Finally, we examine how vaccines may enhance immune suppression of autoimmunity through the upregulation of IDO biosynthesis in human dendritic cells. Full article
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Open AccessReview
Gas Vesicle Nanoparticles for Antigen Display
Vaccines 2015, 3(3), 686-702; https://doi.org/10.3390/vaccines3030686 - 07 Sep 2015
Cited by 12 | Viewed by 3029
Abstract
Microorganisms like the halophilic archaeon Halobacterium sp. NRC-1 produce gas-filled buoyant organelles, which are easily purified as protein nanoparticles (called gas vesicles or GVNPs). GVNPs are non-toxic, exceptionally stable, bioengineerable, and self-adjuvanting. A large gene cluster encoding more than a dozen proteins has [...] Read more.
Microorganisms like the halophilic archaeon Halobacterium sp. NRC-1 produce gas-filled buoyant organelles, which are easily purified as protein nanoparticles (called gas vesicles or GVNPs). GVNPs are non-toxic, exceptionally stable, bioengineerable, and self-adjuvanting. A large gene cluster encoding more than a dozen proteins has been implicated in their biogenesis. One protein, GvpC, found on the exterior surface of the nanoparticles, can accommodate insertions near the C-terminal region and results in GVNPs displaying the inserted sequences on the surface of the nanoparticles. Here, we review the current state of knowledge on GVNP structure and biogenesis as well as available studies on immunogenicity of pathogenic viral, bacterial, and eukaryotic proteins and peptides displayed on the nanoparticles. Recent improvements in genetic tools for bioengineering of GVNPs are discussed, along with future opportunities and challenges for development of vaccines and other applications. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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Open AccessReview
Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy
Vaccines 2015, 3(3), 662-685; https://doi.org/10.3390/vaccines3030662 - 27 Aug 2015
Cited by 103 | Viewed by 7306
Abstract
Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes [...] Read more.
Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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Open AccessArticle
Small Wonders—The Use of Nanoparticles for Delivering Antigen
Vaccines 2015, 3(3), 638-661; https://doi.org/10.3390/vaccines3030638 - 10 Aug 2015
Cited by 11 | Viewed by 2828
Abstract
Despite the discovery of many potential antigens for subunit vaccines, universal protection is often lacking due to the limitations of conventional delivery methods. Subunit vaccines primarily induce antibody-mediated humoral responses, whereas potent antigen-specific cellular responses are required for prevention against some pathogenic infections. [...] Read more.
Despite the discovery of many potential antigens for subunit vaccines, universal protection is often lacking due to the limitations of conventional delivery methods. Subunit vaccines primarily induce antibody-mediated humoral responses, whereas potent antigen-specific cellular responses are required for prevention against some pathogenic infections. Nanoparticles have been utilised in nanomedicine and are promising candidates for vaccine or drug delivery. Nanoparticle vehicles have been demonstrated to be efficiently taken up by dendritic cells and induce humoral and cellular responses. This review provides an overview of nanoparticle vaccine development; in particular, the preparation of nanoparticles using a templating technique is highlighted, which would alleviate some of the disadvantages of existing nanoparticles. We will also explore the cellular fate of nanoparticle vaccines. Nanoparticle-based antigen delivery systems have the potential to develop new generation vaccines against currently unpreventable infectious diseases. Full article
(This article belongs to the Special Issue Vaccine Delivery)
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Open AccessReview
Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants
Vaccines 2015, 3(3), 620-637; https://doi.org/10.3390/vaccines3030620 - 05 Aug 2015
Cited by 26 | Viewed by 3409
Abstract
Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; [...] Read more.
Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
Open AccessReview
Cancer Dormancy: A Regulatory Role for Endogenous Immunity in Establishing and Maintaining the Tumor Dormant State
Vaccines 2015, 3(3), 597-619; https://doi.org/10.3390/vaccines3030597 - 30 Jul 2015
Cited by 27 | Viewed by 3257
Abstract
The significant contribution of host immunity in early tumorigenesis has been recently recognized as a result of our better understanding of the molecular pathways regulating tumor cell biology and tumor-lymphocyte interactions. Emerging evidence suggests that disseminated dormant tumor cells derived from primary tumors [...] Read more.
The significant contribution of host immunity in early tumorigenesis has been recently recognized as a result of our better understanding of the molecular pathways regulating tumor cell biology and tumor-lymphocyte interactions. Emerging evidence suggests that disseminated dormant tumor cells derived from primary tumors before or after immune surveillance, are responsible for subsequent metastases. Recent trends from the field of onco-immunology suggest that efficiently stimulating endogenous anticancer immunity is a prerequisite for the successful outcome of conventional cancer therapies. Harnessing the immune system to achieve clinical efficacy is realistic in the context of conventional therapies resulting in immunogenic cell death and/or immunostimulatory side effects. Targeted therapies designed to target oncogenic pathways in tumor cells can also positively regulate the endogenous immune response and tumor microenvironment. Identification of T cell inhibitory signals has prompted the development of immune checkpoint inhibitors, which specifically hinder immune effector inhibition, reinvigorating and potentially expanding the preexisting anticancer immune response. This anticancer immunity can be amplified in the setting of immunotherapies, mostly in the form of vaccines, which boost naturally occurring T cell clones specifically recognizing tumor antigens. Thus, a promising anticancer therapy will aim to activate patients’ naturally occurring anticancer immunity either to eliminate residual tumor cells or to prolong dormancy in disseminated tumor cells. Such an endogenous anticancer immunity plays a significant role for controlling the balance between dormant tumor cells and tumor escape, and restraining metastases. In this review, we mean to suggest that anticancer therapies aiming to stimulate the endogenous antitumor responses provide the concept of the therapeutic management of cancer. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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Open AccessReview
Cholera Toxin Subunit B as Adjuvant––An Accelerator in Protective Immunity and a Break in Autoimmunity
Vaccines 2015, 3(3), 579-596; https://doi.org/10.3390/vaccines3030579 - 24 Jul 2015
Cited by 44 | Viewed by 3055
Abstract
Cholera toxin subunit B (CTB) is the nontoxic portion of cholera toxin. Its affinity to the monosialotetrahexosylganglioside (GM1) that is broadly distributed in a variety of cell types including epithelial cells of the gut and antigen presenting cells, macrophages, dendritic cells, and B [...] Read more.
Cholera toxin subunit B (CTB) is the nontoxic portion of cholera toxin. Its affinity to the monosialotetrahexosylganglioside (GM1) that is broadly distributed in a variety of cell types including epithelial cells of the gut and antigen presenting cells, macrophages, dendritic cells, and B cells, allows its optimal access to the immune system. CTB can easily be expressed on its own in a variety of organisms, and several approaches can be used to couple it to antigens, either by genetic fusion or by chemical manipulation, leading to strongly enhanced immune responses to the antigens. In autoimmune diseases, CTB has the capacity to evoke regulatory responses and to thereby dampen autoimmune responses, in several but not all animal models. It remains to be seen whether the latter approach translates to success in the clinic, however, the versatility of CTB to manipulate immune responses in either direction makes this protein a promising adjuvant for vaccine development. Full article
(This article belongs to the Special Issue Vaccine Delivery)
Open AccessArticle
Addressing the Vaccine Hesitancy Continuum: An Audience Segmentation Analysis of American Adults Who Did Not Receive the 2009 H1N1 Vaccine
Vaccines 2015, 3(3), 556-578; https://doi.org/10.3390/vaccines3030556 - 15 Jul 2015
Cited by 4 | Viewed by 3029
Abstract
Understanding the heterogeneity of groups along the vaccine hesitancy continuum presents an opportunity to tailor and increase the impact of public engagement efforts with these groups. Audience segmentation can support these goals, as demonstrated here in the context of the 2009 H1N1 vaccine. [...] Read more.
Understanding the heterogeneity of groups along the vaccine hesitancy continuum presents an opportunity to tailor and increase the impact of public engagement efforts with these groups. Audience segmentation can support these goals, as demonstrated here in the context of the 2009 H1N1 vaccine. In March 2010, we surveyed 1569 respondents, drawn from a nationally representative sample of American adults, with oversampling of racial/ethnic minorities and persons living below the United States Federal Poverty Level. Guided by the Structural Influence Model, we assessed knowledge, attitudes, and behaviors related to H1N1; communication outcomes; and social determinants. Among those who did not receive the vaccine (n = 1166), cluster analysis identified three vaccine-hesitant subgroups. Disengaged Skeptics (67%) were furthest from vaccine acceptance, with low levels of concern and engagement. The Informed Unconvinced (19%) were sophisticated consumers of media and health information who may not have been reached with information to motivate vaccination. The Open to Persuasion cluster (14%) had the highest levels of concern and motivation and may have required engagement about vaccination broadly. There were significant sociodemographic differences between groups. This analysis highlights the potential to use segmentation techniques to identify subgroups on the vaccine hesitancy continuum and tailor public engagement efforts accordingly. Full article
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Open AccessReview
Systems Biology Approach for Cancer Vaccine Development and Evaluation
Vaccines 2015, 3(3), 544-555; https://doi.org/10.3390/vaccines3030544 - 14 Jul 2015
Cited by 8 | Viewed by 2711
Abstract
Therapeutic cancer vaccines do not hold promise yet as an effective anti-cancer treatment. Lack of efficacy or poor clinical outcomes are due to several antigenic and immunological aspects that need to be addressed in order to reverse such trends and significantly improve cancer [...] Read more.
Therapeutic cancer vaccines do not hold promise yet as an effective anti-cancer treatment. Lack of efficacy or poor clinical outcomes are due to several antigenic and immunological aspects that need to be addressed in order to reverse such trends and significantly improve cancer vaccines’ efficacy. The newly developed high throughput technologies and computational tools are instrumental to this aim allowing the identification of more specific antigens and the comprehensive analysis of the innate and adaptive immunities. Here, we review the potentiality of systems biology in providing novel insights in the mechanisms of the action of vaccines to improve their design and effectiveness. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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Open AccessArticle
Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC)
Vaccines 2015, 3(3), 519-543; https://doi.org/10.3390/vaccines3030519 - 06 Jul 2015
Cited by 9 | Viewed by 3140
Abstract
Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC) and triple-negative breast cancer (TNBC). Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate [...] Read more.
Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC) and triple-negative breast cancer (TNBC). Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate that rationally designed peptide vaccines/mimics are a viable therapeutic strategy for blocking aberrant molecular signaling pathways with high affinity, specificity, potency and safety. Specifically, we postulate that novel combination treatments targeting members of the EGFR family and IGF-1R will yield significant anti-tumor effects in in vitro models of EC and TNBC possibly overcoming mechanisms of resistance. We show that the combination of HER-1 and HER-2 or HER-1 and IGF-1R peptide mimics/vaccine antibodies exhibited enhanced antitumor properties with significant inhibition of tumorigenesis in OE19 EC and MDA-MB-231 TNBC cell lines. Our work elucidates the mechanisms of HER-1/IGF-1R and HER-1/HER-2 signaling in these cancer cell lines, and the promising results support the rationale for dual targeting with HER-1 and HER-2 or IGF-1R as an improved treatment regimen for advanced therapy tailored to difference types of cancer. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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Open AccessArticle
Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
Vaccines 2015, 3(3), 503-518; https://doi.org/10.3390/vaccines3030503 - 03 Jul 2015
Cited by 12 | Viewed by 2795
Abstract
Vaccines against dengue virus (DV) are commercially nonexistent. A subunit vaccination strategy may be of value, especially if a safe viral vector acts as biologically active adjuvant. In this paper, we focus on an immunoglobulin-like, independently folded domain III (DIII) from DV 2 [...] Read more.
Vaccines against dengue virus (DV) are commercially nonexistent. A subunit vaccination strategy may be of value, especially if a safe viral vector acts as biologically active adjuvant. In this paper, we focus on an immunoglobulin-like, independently folded domain III (DIII) from DV 2 envelope protein (E), which contains epitopes that elicits highly specific neutralizing antibodies. We modified the hepatitis B small surface antigen (HBsAg, S) in order to display DV 2 DIII on a virus-like particle (VLP), thus generating the hybrid antigen DIII-S. Two varieties of measles virus (MV) vectors were developed to express DIII-S. The first expresses the hybrid antigen from an additional transcription unit (ATU) and the second additionally expresses HBsAg from a separate ATU. We found that this second MV vectoring the hybrid VLPs displaying DIII-S on an unmodified HBsAg scaffold were immunogenic in MV-susceptible mice (HuCD46Ge-IFNarko), eliciting robust neutralizing responses (averages) against MV (1:1280 NT90), hepatitis B virus (787 mIU/mL), and DV2 (1:160 NT50) in all of the tested animals. Conversely, the MV vector expressing only DIII-S induced immunity against MV alone. In summary, DV2 neutralizing responses can be generated by displaying E DIII on a scaffold of HBsAg-based VLPs, vectored by MV. Full article
(This article belongs to the Special Issue Dengue Vaccines)
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Open AccessReview
Interest of Tumor-Specific CD4 T Helper 1 Cells for Therapeutic Anticancer Vaccine
Vaccines 2015, 3(3), 490-502; https://doi.org/10.3390/vaccines3030490 - 30 Jun 2015
Cited by 23 | Viewed by 2552
Abstract
Nowadays, immunotherapy represents one promising approach for cancer treatment. Recently, spectacular results of cancer immunotherapy clinical trials have confirmed the crucial role of immune system in cancer regression. Therapeutic cancer vaccine represents one widely used immunotherapy strategy to stimulate tumor specific T cell [...] Read more.
Nowadays, immunotherapy represents one promising approach for cancer treatment. Recently, spectacular results of cancer immunotherapy clinical trials have confirmed the crucial role of immune system in cancer regression. Therapeutic cancer vaccine represents one widely used immunotherapy strategy to stimulate tumor specific T cell responses but clinical impact remains disappointing in targeting CD8 T cells. Although CD8 T cells have been initially considered to be the main protagonists, it is now clear that CD4 T cells also play a critical role in antitumor response. In this article, we discuss the role of tumor antigen-specific CD4 T cell responses and how we can target these cells to improve cancer vaccines. Full article
(This article belongs to the Special Issue Cancer Vaccines)
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