Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Lopes, Alessandra; Vanvarenberg, Kévin; Kos, Špela; Lucas, Sophie; Colau, Didier; Eynde, Benoı̂t Van den; Préat, Véronique; Vandermeulen, Gaëlle

doi:10.1038/s41598-018-33933-7

Cited by 23 publications

(22 citation statements)

References 52 publications

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“…These data suggest that the combination of DNA vaccination and immune checkpoint blockade is crucial for activation and infiltration of antigen-specific CD8 + locally at the tumor site, which is crucial for successful elimination of tumor cells. Similar results were obtained in our previously published study using DNA vaccine against murine P815 mastocytoma in combination with immune checkpoint blockade [24].…”

Section: Resultssupporting

confidence: 91%

Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma

et al. 2019

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We aimed to explore whether the combination of intradermal DNA vaccination, to boost immune response against melanoma antigens, and immune checkpoint blockade, to alleviate immunosuppression, improves antitumor effectiveness in a murine B16F10 melanoma tumor model. Compared to single treatments, a combination of intradermal DNA vaccination (ovalbumin or gp100 plasmid adjuvanted with IL12 plasmid) and immune checkpoint CTLA-4/PD-1 blockade resulted in a significant delay in tumor growth and prolonged survival of treated mice. Strong activation of the immune response induced by combined treatment resulted in a significant antigen-specific immune response, with elevated production of antigen-specific IgG antibodies and increased intratumoral CD8 + infiltration. These results indicate a potential application of the combined DNA vaccination and immune checkpoint blockade, specifically, to enhance the efficacy of DNA vaccines and to overcome the resistance to immune checkpoint inhibitors in certain cancer types.

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Section: Resultssupporting

confidence: 91%

Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma

et al. 2019

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“…Some examples include combination with radiation therapy [105], other antibodies [106], photodynamic therapy [107], and cancer vaccines [108]. Combination with cancer DNA vaccination seems to be promising in coupling the benefits of ICB with the ability of vaccines to prime the antigen-specific CTL response [88, 109]. A potent cancer vaccine that induces a T cell response against tumor-specific antigens could also increase the number of responders to ICB [63].…”

Section: Introductionmentioning

confidence: 99%

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Lopes

Vandermeulen

Préat

2019

J Exp Clin Cancer Res

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263

162

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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 and the activation of a broad and specific immune response. However, these vaccines often demonstrated only modest therapeutic effects in clinical trials due to the immunosuppressive mechanisms developed by the tumor. To enhance the vaccine-induced immune response and the treatment efficacy, DNA vaccines could be improved by using two different strategies. The first is to increase their immunogenicity by selecting and optimizing the best antigen(s) to be inserted into the plasmid DNA. The second strategy is to combine DNA vaccines with other complementary therapies that could improve their activity by attenuating immunosuppression in the tumor microenvironment or by increasing the activity/number of immune cells. A growing number of preclinical and clinical studies are adopting these two strategies to better exploit the potential of DNA vaccination. In this review, we analyze the last 5-year preclinical studies and 10-year clinical trials using plasmid DNA vaccines for cancer therapy. We also investigate the strategies that are being developed to overcome the limitations in cancer DNA vaccination, revisiting the rationale for different combinations of therapy and the different possibilities in antigen choice. Finally, we highlight the most promising developments and critical points that need to be addressed to move towards the approval of therapeutic cancer DNA vaccines as part of the standard of cancer care in the future.

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“…8,17,18 Conversely, checkpoint blockade therapy may improve the effector function of vaccine-induced T cells once they home to the immunosuppressive tumor microenvironment. 25,26 Thus, while immunotherapies have yet to translate into improved survival for patients with GBM, a combinatorial immune-based approach may lead to better outcomes in the future.…”

Section: Discussionmentioning

confidence: 99%

Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma

et al. 2019

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Neoantigens represent promising targets for personalized cancer vaccine strategies. However, the feasibility of this approach in lower mutational burden tumors like glioblastoma (GBM) remains unknown. We have previously reported the use of an immunogenomics pipeline to identify candidate neoantigens in preclinical models of GBM. Here, we report the application of the same immunogenomics pipeline to identify candidate neoantigens and guide screening for neoantigen-specific T cell responses in a patient with GBM treated with a personalized synthetic long peptide vaccine following autologous tumor lysate DC vaccination. Following vaccination, reactivity to three HLA class I-and five HLA class II-restricted candidate neoantigens were detected by IFN-γ ELISPOT in peripheral blood. A similar pattern of reactivity was observed among isolated post-treatment tumor-infiltrating lymphocytes. Genomic analysis of pre-and post-treatment GBM reflected clonal remodeling. These data demonstrate the feasibility and translational potential of a therapeutic neoantigen-based vaccine approach in patients with primary CNS tumors.

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Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Cited by 23 publications

References 52 publications

Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma

Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma

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