A multi-trimeric fusion of CD40L and gp100 tumor antigen activates dendritic cells and enhances survival in a B16-F10 melanoma DNA vaccine model

Gupta, Sachin; Termini, James M.; Rivas, Yaelis; Otero, Miguel; Raffa, Francesca; Bhat, Vikas; Farooq, Amjad; Stone, Geoffrey W.

doi:10.1016/j.vaccine.2015.07.081

Cited by 19 publications

(16 citation statements)

References 45 publications

(62 reference statements)

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“…Its great efficacy against metastatic melanoma and metastatic renal cell carcinoma led to its approval by the FDA [7, 93]. IL-12 is another important cytokine involved in T cell activation and effector function, and its combination with a vaccine increases the vaccine’s efficacy [94]. A plasmid encoding IL-12 combined with a DNA vaccine against cervical cancer promoted mouse survival and decreased the number of MDSCs in the TME [95].…”

Section: Introductionmentioning

confidence: 99%

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

Lopes

Vandermeulen

Préat

2019

J Exp Clin Cancer Res

288

203

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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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Section: Introductionmentioning

confidence: 99%

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

Lopes

Vandermeulen

Préat

2019

J Exp Clin Cancer Res

288

203

View full text Add to dashboard Cite

show abstract

“…While not explicitly oncolytic viruses, presumably the efficacy of these approaches engages some element of antigen release by viral lytic activity and the additional innate sensing pathways activated by viral infection of cancer cells, in combination with myeloid cell activation by CD40 stimulation. Further formulations to achieve CD40 stimulation include recombinant proteins with natural trimer conformation [ 81 ], or in some instances hexamer construction [ 82 ], with the goal of more naturally and potently inducing CD40 signaling without accompanying cytokine storm toxicity that has been evident with antibody-mediated stimulation. It should be noted that some discussion is ongoing about the relative effectiveness of different CD40 cross-linking antibodies being dependent upon Fc receptor-mediated binding.…”

Section: Delivery Formats For Cd40mentioning

confidence: 99%

CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies

Bullock

2021

Cell Mol Immunol

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The substantial advances attained by checkpoint blockade immunotherapies have driven an expansion in the approaches used to promote T cell access to the tumor microenvironment to provide targets for checkpoint immunotherapy. Inherent in any T cell response to a tumor antigen is the capacity of dendritic cells to initiate and support such responses. Here, the rationale and early immunobiology of CD40 as a master regulator of dendritic cell activation is reviewed, with further contextualization and appreciation for the role of CD40 stimulation not only in cancer vaccines but also in other contemporary immune-oncology approaches.

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“…However, expressing it in RM1 provides a well‐defined immune target with tools to monitor the tumor‐specific cellular immune response. To generate an immune response against gp100, active measures are required to generate a gp100‐specific response 21,22 . For example, in our study, gp100 was pulsed onto fresh DCs, which were then able to home to mouse lymph nodes and activate CD8 T cells, ultimately resulting in tumor control.…”

Section: Discussionmentioning

confidence: 99%

Syngeneic murine model for prostate cancer using RM1 cells transfected with gp100

Yeon

Wang

et al. 2020

The Prostate

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Background Prostate cancer (PC) is the most commonly diagnosed solid tumor in men. A major challenge in PC immunotherapy is the lack of an animal model that resembles human adenocarcinoma and allows for manipulation or monitoring of the immune response. Mouse models are needed for preclinical testing of new immunotherapies, whether used alone or in combination with established drugs, and to develop companion biomarkers that can be validated in clinical trials. Methods To develop a syngeneic prostate adenocarcinoma model with a well‐defined tumor antigen, murine RM1 PC cells were transfected with the endogenous mouse melanoma protein, gp100 (RM1‐gp100). Gp100 was attractive because it is a self‐protein and it instantly allowed us to use the large trove of immune research tools developed for melanoma research. A dendritic cell (DC) vaccine was used as model immunotherapy to demonstrate that adoptive immunotherapy against gp100 decreases the growth of RM1‐gp100 but not RM1. Results Expressing gp100 did not change the growth of RM1 cell in vitro or in vivo. The DCs pulsed with RM1‐gp100 could be used to stimulate Pmel‐1 lymphocyte proliferation and activation. Pmel‐1 lymphocytes could be adoptively transferred into C57Bl/6 mice that were treated with DCs pulsed with RM1‐gp100. The resulting Pmel‐1 lymphocytes were monitored to assess the primary cellular immune response and memory response. Conclusion We describe a murine model for prostate adenocarcinoma with a well‐characterized antigen that can be used in an immunologically intact mice to monitor the temporal CD8+ lymphocyte‐mediated antitumor immunity.

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A multi-trimeric fusion of CD40L and gp100 tumor antigen activates dendritic cells and enhances survival in a B16-F10 melanoma DNA vaccine model

Cited by 19 publications

References 45 publications

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

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

CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies

Syngeneic murine model for prostate cancer using RM1 cells transfected with gp100

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