Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape

Garg, Abhishek D.; Coulie, Pierre G.; Eynde, Benoı̂t J. Van den; Agostinis, Patrizia

doi:10.1016/j.it.2017.05.006

Cited by 292 publications

(280 citation statements)

References 97 publications

(160 reference statements)

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“…From a small amount of peripheral blood, one can usually obtain sufficient numbers (approximately 1 × 10 5 to 1 × 10 7 cells/kg body weight) of activated antigen-presenting B cells [35, 51], whereas the generation of DCs typically requires a leukapheresis [52-55]. It has been shown that this is even feasible in cancer patients [35, 51].…”

Section: B Cells For Immunotherapymentioning

confidence: 99%

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B Cell-Based Cancer Immunotherapy

Wennhold

Shimabukuro‐Vornhagen

Bergwelt‐Baildon

2019

Transfus Med Hemother

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B cells are not only producers of antibodies, but also contribute to immune regulation or act as potent antigen-presenting cells. The potential of B cells for cellular therapy is still largely underestimated, despite their multiple diverse effector functions. The CD40L/CD40 signaling pathway is the most potent activator of antigen presentation capacity in B lymphocytes. CD40-activated B cells are potent antigen-presenting cells that induce specific T-cell responses in vitro and in vivo. In preclinical cancer models in mice and dogs, CD40-activated B cell-based cancer immunotherapy was able to induce effective antitumor immunity. So far, there have been only few early-stage clinical studies involving B cell-based cancer vaccines. These trials indicate that B cell-based immunotherapy is generally safe and associated with little toxicity. Furthermore, these studies suggest that B-cell immunotherapy can elicit antitumor T-cell responses. Alongside the recent advances in cellular therapies in general, major obstacles for generation of good manufacturing practice-manufactured B-cell immunotherapies have been overcome. Thus, a first clinical trial involving CD40-activated B cells might be in reach.

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Section: B Cells For Immunotherapymentioning

confidence: 99%

“…However, the current excitement about the success of immune checkpoint blockade in the treatment of a broad range of malignancies has sparked a renaissance of cancer vaccines [52]. Currently, several clinical trials are investigating the combination of DC vaccines with checkpoint inhibitors.…”

Section: Future Perspectivesmentioning

confidence: 99%

B Cell-Based Cancer Immunotherapy

Wennhold

Shimabukuro‐Vornhagen

Bergwelt‐Baildon

2019

Transfus Med Hemother

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“…Cancer vaccines are aimed at inducing durable anti‐tumor immunity for systemic protection against tumor recurrence or metastasis . Various anti‐glioma vaccines have been developed; one strategy involves the administration of dendritic cell (DC)‐based vaccines, in particular, autologous DCs containing glioma‐associated peptides or whole tumor lysate.…”

Section: Introductionmentioning

confidence: 99%

An effective dendritic cell‐based vaccine containing glioma stem‐like cell lysate and CpG adjuvant for an orthotopic mouse model of glioma

Zhu

Zhang

et al. 2019

Intl Journal of Cancer

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Owing to the limited therapeutic efficacy of glioma vaccines, new strategies are required to improve cancer vaccines. Our study aimed to assess the therapeutic efficacy of a glioma vaccine called STDENVANT. This vaccine, comprising glioma stem‐like cell (GSC) lysate, dendritic cells (DCs), and Toll‐like receptor (TLR) 9 agonist CpG motif‐containing oligodeoxynucleotides (CpG ODNs), was assessed using a GL261‐C57BL/6 orthotopic mouse model of glioma. STDENVANT markedly improved survival and tumor regression by enhancing anti‐tumor immune function. Moreover, STDENVANT upregulated programmed death 1 (PD‐1) and its ligand PD‐L1 on effector T cells, DCs, and glioma tissues, resulting in the accumulation of regulatory T (Treg) cells in the brain and lymph nodes. Combinatorial administration of anti‐PD‐L1 antibody and STDENVANT conferred a greater survival advantage and decreased the Treg cell population in the brain. The present results indicate that PD‐L1 blockade can promote tumor regression via STDENVANT in a mouse model of glioma, and combinatorial administration of anti‐PD‐L1 antibody and STDENVANT increases the therapeutic anti‐tumor efficacy of treatment.

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“…The safety and ability to induce antitumor responses have clearly been established for DC vaccination and patients with long‐term benefit have been reported . Still, DC vaccines have not yet fulfilled their promise and still face several challenges as only a small number of injected DCs migrate to draining lymph nodes and their optimal activation is critical . Recent evidence from DC‐based vaccinations against melanoma suggests that efficacy depends on several factors such as the mode of antigen loading, the maturation‐state of the DCs, the site of injection and the vaccination schedule .…”

Section: Introductionmentioning

confidence: 99%

Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment

Koske

Rössler

Pipperger

et al. 2019

Intl Journal of Cancer

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The efficacy of cancer vaccines has been limited by the immunosuppressive tumor microenvironment, which can be alleviated by immune checkpoint inhibitor (ICI) therapy. Here, we tested if oncolytic viruses (OVs), similar to ICI, can also synergize with cancer vaccines by modulating the tumor microenvironment. VSV‐GP, a chimeric vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. Here, we show that in mouse B16‐OVA melanoma, combination treatment of VSV‐GP with an ovalbumin (OVA) peptide‐loaded dendritic cell (DC) vaccine (DCVacc) significantly enhanced survival over the single agent therapies, although both DCVacc and DCVacc/VSV‐GP treatments induced comparable levels of OVA‐specific CD8 T cell responses. Virus replication was minimal so that direct viral oncolysis in B16‐OVA did not contribute to this synergism. The strong therapeutic effect of the DCVacc/VSV‐GP combination treatment was associated with high numbers of tumor‐infiltrating, highly activated T cells and the relative reduction of regulatory T cells in treated and contra‐lateral nontreated tumors. Accordingly, depletion of CD8 T cells but not natural killer cells abrogated the therapeutic effect of DCVacc/VSV‐GP supporting the crucial role of CD8 T cells. In addition, a drastic increase in several proinflammatory cytokines was observed in VSV‐GP‐treated tumors. Taken together, OVs, similar to ICI, have the potential to markedly increase the efficacy of cancer vaccines by alleviating local immune suppression in the tumor microenvironment.

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Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape

Cited by 292 publications

References 97 publications

B Cell-Based Cancer Immunotherapy

B Cell-Based Cancer Immunotherapy

An effective dendritic cell‐based vaccine containing glioma stem‐like cell lysate and CpG adjuvant for an orthotopic mouse model of glioma

Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment

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