A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model

Julius W. Kim, J. Robert Kane, Wojciech K. Panek, Jacob S. Young, Aida Rashidi, Dou Yu, Deepak Kanojia, Tanwir Hasan, Jason Michael Miska, Miguel A. Gómez-Lim, Ilya Ulasov, Irina V Balyasnikova, Atique Uddin Ahmed, Derek Alan Wainwright, Maciej S Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body’s most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261 CMV-IE -implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.

Original languageEnglish (US)
Pages (from-to)1127-1138
Number of pages12
JournalNeurotherapeutics
Volume15
Issue number4
DOIs
StatePublished - Oct 14 2018

Fingerprint

Adaptive Immunity
Glioma
Dendritic Cells
Antigens
Survival
Neoplasms
Immunization
Cell Surface Receptors
Neoplasm Antigens
Antigen-Presenting Cells
Vaccination
T-Lymphocytes
Infection

Keywords

  • adenovirus
  • cytomegalovirus
  • dendritic cells
  • glioblastoma
  • vaccine

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

Cite this

Kim, Julius W. ; Kane, J. Robert ; Panek, Wojciech K. ; Young, Jacob S. ; Rashidi, Aida ; Yu, Dou ; Kanojia, Deepak ; Hasan, Tanwir ; Miska, Jason Michael ; Gómez-Lim, Miguel A. ; Ulasov, Ilya ; Balyasnikova, Irina V ; Ahmed, Atique Uddin ; Wainwright, Derek Alan ; Lesniak, Maciej S. / A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model. In: Neurotherapeutics. 2018 ; Vol. 15, No. 4. pp. 1127-1138.
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abstract = "Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body’s most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60{\%} of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10{\%}, demonstrating superior infectivity on DCs. Moreover, an average of 14{\%} of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3{\%} of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261 CMV-IE -implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.",
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A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model. / Kim, Julius W.; Kane, J. Robert; Panek, Wojciech K.; Young, Jacob S.; Rashidi, Aida; Yu, Dou; Kanojia, Deepak; Hasan, Tanwir; Miska, Jason Michael; Gómez-Lim, Miguel A.; Ulasov, Ilya; Balyasnikova, Irina V; Ahmed, Atique Uddin; Wainwright, Derek Alan; Lesniak, Maciej S.

In: Neurotherapeutics, Vol. 15, No. 4, 14.10.2018, p. 1127-1138.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model

AU - Kim, Julius W.

AU - Kane, J. Robert

AU - Panek, Wojciech K.

AU - Young, Jacob S.

AU - Rashidi, Aida

AU - Yu, Dou

AU - Kanojia, Deepak

AU - Hasan, Tanwir

AU - Miska, Jason Michael

AU - Gómez-Lim, Miguel A.

AU - Ulasov, Ilya

AU - Balyasnikova, Irina V

AU - Ahmed, Atique Uddin

AU - Wainwright, Derek Alan

AU - Lesniak, Maciej S

PY - 2018/10/14

Y1 - 2018/10/14

N2 - Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body’s most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261 CMV-IE -implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.

AB - Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body’s most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261 CMV-IE -implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.

KW - adenovirus

KW - cytomegalovirus

KW - dendritic cells

KW - glioblastoma

KW - vaccine

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