Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models

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Fotaki, GrammatikiUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi (author)

Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models

Article/chapterEnglish2018

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2018
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LIBRIS-ID:oai:DiVA.org:uu-346362
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-346362URI
https://doi.org/10.1080/2162402X.2017.1397250DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Autologous patient-derived dendritic cells (DCs) modified ex vivo to present tumor-associated antigens (TAAs) are frequently used as cancer vaccines. However, apart from the stringent logistics in producing DCs on a patient basis, accumulating evidence indicate that ex vivo engineered DCs are poor in migration and in fact do not directly present TAA epitopes to naïve T cells in vivo. Instead, it is proposed that bystander host DCs take up material from vaccine-DCs, migrate and subsequently initiate antitumor T-cell responses. We used mouse models to examine the possibility of using pro-inflammatory allogeneic DCs (alloDCs) to activate host DCs and enable them to promote antigen-specific T-cell immunity. We found that alloDCs were able to initiate host DC activation and migration to draining lymph node leading to T-cell activation. The pro-inflammatory milieu created by alloDCs also led to recruitment of NK cells and neutrophils at the site of injection. Vaccination with alloDCs combined with Ad5M(gp100), an infection-enhanced adenovirus encoding the human melanoma-associated antigen gp100 resulted in generation of CD8+ T cells with a T-cell receptor (TCR) specific for the gp10025-33 epitope (gp100-TCR+). Ad5M(gp100)-alloDC vaccination in combination with transfer of gp100-specific pmel-1 T cells resulted in prolonged survival of B16-F10 melanoma-bearing mice and altered the composition of the tumor microenvironment (TME). We hereby propose that alloDCs together with TAA- or neoepitope-encoding Ad5M can become an “off-the-shelf” cancer vaccine, which can reverse the TME-induced immunosuppression and induce host cellular anti-tumor immune responses in patients without the need of a time-consuming preparation step of autologous DCs.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
adjuvants
Allogeneic dendritic cells
cell-based immunotherapy
tumor microenvironment
tumor-associated antigen

Added entries (persons, corporate bodies, meetings, titles ...)

Jin, Chuan,1986-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)chuji162 (author)
Kerzeli, Iliana KyriakiUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)iliky579 (author)
Ramachandran, Mohanraj,1988-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)mohra272 (author)
Martikainen, Minttu-MariaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)minma327 (author)
Karlsson-Parra, AlexUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Immunicum AB, Gothenburg(Swepub:uu)aka12694 (author)
Yu, Di,1985-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)diayu422 (author)
Essand, MagnusUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)magnessa (author)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

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In:Oncoimmunology7:32162-40112162-402X

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