Special Issue "Therapeutic Vaccines and Cancer Immunotherapy"

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 May 2018)

Special Issue Editor

Guest Editor
Prof. Dr. C.A.H.H. (Toos) Daemen

Department of Medical Microbiology, University of Groningen, Groningen 9700 RB, The Netherlands
Website | E-Mail
Phone: +31-50-361-6560
Interests: cancer immunotherapy; therapeutic vaccines; HPV; Hepatitis C virus; intratumoral immune environment; alphavirus-based vaccines

Special Issue Information

Dear Colleagues,

In this Special Issue of Vaccines, we will focus on strategies based on cancer vaccines, either as single agent treatments or combined with other therapeutic cancer treatments. A multitude of cancer vaccines have shown promising results in preclinical studies, but so far only one cancer vaccine is FDA approved. This is remarkable given the fact that in general antigen-specific immune cells are elicited, also in clinical trials. One can envision several reasons for the somewhat limiting clinical results. Reasons that put forward new challenges to achieve clinical effective therapeutic cancer vaccines. First, limited clinical responses may be due to insufficient or inappropriate activation of antigen-specific immune effector cells in cancer patients due to immune tolerance and immune suppression. Second, therapeutic efficacy might be hampered by the immune suppressive microenvironment in the tumor. Immune-effector cells may either be unable to accumulate into tumors or are inactivated rapidly upon infiltrating into a tumor. Thus, research on further improvements to pre-emptively increase the chance of therapeutic efficacy of cancer vaccines in the clinic is still essential.

It is becoming increasingly more apparent that, as part of the design of vaccine regimens, combination therapy might be a better treatment option compared to monotherapy for durable clinical responses. Combination regimens currently being explored include differing immunotherapeutic approaches including vaccines combined with conventional chemotherapy and radiation therapy. A more in-depth understanding on effects of dosing and scheduling of these treatments is required for a rational design of therapeutic combinations. In addition, especially in this era of check-point blockade immunotherapy and targeted therapies, cancer vaccines are regaining major clinical interest, as induction and/or expansion of tumor-specific immune effector cells will be vital to further enhance and broaden the efficacy and applicability of these forms of cancer immunotherapies.

In this Special Issue, we hope to provide an overview on novel or optimized cancer vaccines and rational combination therapies that aim to further enhance numbers, activity and recruitment of immune effector cells in the tumor microenvironment.

Prof. Dr. C.A.H.H. (Toos) Daemen
Guest Editor

Manuscript Submission Information

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Keywords

  • Therapeutic cancer vaccine
  • Vaccine optimization 
  • Immune cell infiltration 
  • Cancer immunotherapy 
  • Combination therapies
  • Anti-tumor activity
  • Tumor suppression 
  • Check point blockade 
  • Targeted therapies 
  • Chemo/radiation

Published Papers (10 papers)

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Research

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Open AccessArticle Improved Induction of Anti-Melanoma T Cells by Adenovirus-5/3 Fiber Modification to Target Human DCs
Received: 30 May 2018 / Revised: 12 July 2018 / Accepted: 16 July 2018 / Published: 18 July 2018
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Abstract
To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs [...] Read more.
To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8+ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. “Off-the-shelf” DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessArticle Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells
Received: 30 May 2018 / Revised: 26 June 2018 / Accepted: 5 July 2018 / Published: 6 July 2018
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Abstract
Hematopoietic stem cells (HSCs) yield both the myeloid and lymphoid lineages of blood cells and can be reprogrammed into tumor antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) to prevent tumor growth. However, the optimal approach for differentiating tumor Ag-specific CTLs from HSCs, [...] Read more.
Hematopoietic stem cells (HSCs) yield both the myeloid and lymphoid lineages of blood cells and can be reprogrammed into tumor antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) to prevent tumor growth. However, the optimal approach for differentiating tumor Ag-specific CTLs from HSCs, such as HSC-CTLs, remains elusive. In the current study, we showed that a combination of genetic modification of HSCs and in vivo T cell development facilitates the generation of Ag-specific CTLs that suppressed tumor growth. Murine HSCs, which were genetically modified with chicken ovalbumin (OVA)-specific T cell receptor, were adoptively transferred into recipient mice. In the following week, mice were administered with intraperitoneal injections of an agonist α-Notch 2 antibody and cytokines (rFlt3L and rIL-7) three times. After another two weeks, mice received a subcutaneous inoculation of B16-OVA melanoma cells that express OVA as a surrogate tumor Ag, before the anti-tumor activity of HSC-derived T cells was assessed. OVA-specific CTLs developed in vivo and greatly responded to OVA Ag stimulation ex vivo. In addition, mice receiving genetically modified HSCs and in vivo priming established anti-tumor immunity, resulting in the suppression of tumor growth. These results reported in this present study provide an alternative strategy to develop protective cancer vaccines by using genetically modified HSCs. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Review

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Open AccessReview Does the Immunocompetent Status of Cancer Patients Have an Impact on Therapeutic DC Vaccination Strategies?
Received: 4 October 2018 / Revised: 9 November 2018 / Accepted: 21 November 2018 / Published: 23 November 2018
Cited by 2 | PDF Full-text (829 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent [...] Read more.
Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent status of cancer patients, which may facilitate tumor development by different mechanisms, including immune evasion. The most frequently used cellular vehicle in clinical trials are dendritic cells (DCs), thanks to their crucial role in initiating and directing immune responses. Viable vaccination options using DCs are available, with a positive toxicity profile. For these reasons, despite their limited therapeutic outcomes, DC vaccination is currently considered an additional immunotherapeutic option that still needs to be further explored. In this review, we propose potential actions aimed at improving DC vaccine efficacy by counteracting the detrimental mechanisms recognized to date and implicated in establishing a poor immunocompetent status in cancer patients. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessReview Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy
Received: 26 July 2018 / Revised: 19 September 2018 / Accepted: 21 September 2018 / Published: 26 September 2018
Cited by 1 | PDF Full-text (1004 KB) | HTML Full-text | XML Full-text
Abstract
Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain molecular constituents of their host cells. They are released from different types of cells ranging from immune to tumor cells and play an important role in intercellular communication. Exosomes [...] Read more.
Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain molecular constituents of their host cells. They are released from different types of cells ranging from immune to tumor cells and play an important role in intercellular communication. Exosomes can be manipulated by altering their host cells and can be loaded with products of interest such as specific drugs, proteins, DNA and RNA species. Due to their small size and the unique composition of their lipid bilayer, exosomes are capable of reaching different cell types where they alter the pathophysiological conditions of the recipient cells. There is growing evidence that exosomes are used as vehicles that can modulate the immune system and play an important role in cancer progression. The cross communication between the tumors and the cells of the immune system has gained attention in various immunotherapeutic approaches for several cancer types. In this review, we discuss the exosome biogenesis, their role in inter-cellular communication, and their capacity to modulate the immune system as a part of future cancer immunotherapeutic approaches and their potential to serve as biomarkers of therapy response. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessReview BDCA1+CD14+ Immunosuppressive Cells in Cancer, a Potential Target?
Received: 27 August 2018 / Revised: 17 September 2018 / Accepted: 18 September 2018 / Published: 19 September 2018
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Abstract
Dendritic cell (DC) vaccines show promising effects in cancer immunotherapy. However, their efficacy is affected by a number of factors, including (1) the quality of the DC vaccine and (2) tumor immune evasion. The recently characterized BDCA1+CD14+ immunosuppressive cells combine both aspects; their [...] Read more.
Dendritic cell (DC) vaccines show promising effects in cancer immunotherapy. However, their efficacy is affected by a number of factors, including (1) the quality of the DC vaccine and (2) tumor immune evasion. The recently characterized BDCA1+CD14+ immunosuppressive cells combine both aspects; their presence in DC vaccines may directly hamper vaccine efficacy, whereas, in patients, BDCA1+CD14+ cells may suppress the induced immune response in an antigen-specific manner systemically and at the tumor site. We hypothesize that BDCA1+CD14+ cells are present in a broad spectrum of cancers and demand further investigation to reveal treatment opportunities and/or improvement for DC vaccines. In this review, we summarize the findings on BDCA1+CD14+ cells in solid cancers. In addition, we evaluate the presence of BDCA1+CD14+ cells in leukemic cancers. Preliminary results suggest that the presence of BDCA1+CD14+ cells correlates with clinical features of acute and chronic myeloid leukemia. Future research focusing on the differentiation from monocytes towards BDCA1+CD14+ cells could reveal more about their cell biology and clinical significance. Targeting these cells in cancer patients may improve the outcome of cancer immunotherapy. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessReview Endometrial Stromal Sarcomas: A Revision of Their Potential as Targets for Immunotherapy
Received: 13 July 2018 / Revised: 17 August 2018 / Accepted: 22 August 2018 / Published: 25 August 2018
Cited by 1 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
Endometrial stromal sarcomas are a subtype of uterine sarcomas that are characterized by recurrent chromosomal translocations, resulting in the expression of tumor-specific fusion proteins that contribute to their tumorigenicity. These characteristics make the translocation breakpoints promising targets for immunotherapeutic approaches. In this review, [...] Read more.
Endometrial stromal sarcomas are a subtype of uterine sarcomas that are characterized by recurrent chromosomal translocations, resulting in the expression of tumor-specific fusion proteins that contribute to their tumorigenicity. These characteristics make the translocation breakpoints promising targets for immunotherapeutic approaches. In this review, we first describe the current knowledge about the classification of endometrial stromal sarcomas, and their molecular and genetic characteristics. Next, we summarize the available data on the use of translocation breakpoints as immunotherapeutic targets. Finally, we propose a roadmap to evaluate the feasibility of immunologic targeting of the endometrial stromal sarcoma-specific translocations in patients with recurrent disease. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessReview Therapeutic Vaccines for Genitourinary Malignancies
Received: 17 July 2018 / Accepted: 6 August 2018 / Published: 12 August 2018
Cited by 1 | PDF Full-text (209 KB) | HTML Full-text | XML Full-text
Abstract
The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval [...] Read more.
The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval of sipuleucel-T for prostate cancer. Several vaccine strategies have emerged, such as autologous or allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides as immunostimulatory adjuvants. Despite impressive early trials, vaccine monotherapy has achieved limited success in the clinical world; however, combinations of vaccine and immune checkpoint inhibition or vaccine and cytokine stimulation are expected to move the field forward. This article reviews pivotal trials of cancer vaccines in prostate, renal, and bladder cancer and ongoing trials combining vaccines with other immune therapy agents. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
Open AccessReview Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis
Received: 13 July 2018 / Revised: 6 August 2018 / Accepted: 6 August 2018 / Published: 10 August 2018
Cited by 1 | PDF Full-text (1654 KB) | HTML Full-text | XML Full-text
Abstract
Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction [...] Read more.
Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessReview Next Generation Cancer Vaccines—Make It Personal!
Received: 8 June 2018 / Revised: 23 July 2018 / Accepted: 7 August 2018 / Published: 9 August 2018
Cited by 1 | PDF Full-text (463 KB) | HTML Full-text | XML Full-text
Abstract
Dramatic success in cancer immunotherapy has been achieved over the last decade with the introduction of checkpoint inhibitors, leading to response rates higher than with chemotherapy in certain cancer types. These responses are often restricted to cancers that have a high mutational burden [...] Read more.
Dramatic success in cancer immunotherapy has been achieved over the last decade with the introduction of checkpoint inhibitors, leading to response rates higher than with chemotherapy in certain cancer types. These responses are often restricted to cancers that have a high mutational burden and show pre-existing T-cell infiltrates. Despite extensive efforts, therapeutic vaccines have been mostly unsuccessful in the clinic. With the introduction of next generation sequencing, the identification of individual mutations is possible, enabling the production of personalized cancer vaccines. Combining immune check point inhibitors to overcome the immunosuppressive microenvironment and personalized cancer vaccines for directing the host immune system against the chosen antigens might be a promising treatment strategy. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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Open AccessReview Listeria monocytogenes as a Vector for Cancer Immunotherapy: Current Understanding and Progress
Received: 22 June 2018 / Revised: 21 July 2018 / Accepted: 23 July 2018 / Published: 25 July 2018
Cited by 1 | PDF Full-text (592 KB) | HTML Full-text | XML Full-text
Abstract
Listeria monocytogenes, a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials [...] Read more.
Listeria monocytogenes, a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials testing Listeria cancer vaccines are currently underway, which will help to understand the utility of Listeria vaccines in cancer immunotherapy. This review aims to summarize current views on how Listeria-based vaccines induce potent antitumor immunity and the current state of Listeria-based cancer vaccines in clinical trials. Full article
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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