Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40

Wenthe, JessicaUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab (författare)

Multiple myeloma (MM) is a plasma cell malignancy that is characterized by immune dysregulation. MM is commonly treated with immunomodulating agents, but still remains incurable. Herein, we proposed and evaluated immunostimulatory Lokon oncolytic adenoviruses (LOAd) for MM treatment. LOAd viruses are serotype 5/35 chimera, which enables infection of hematopoietic cells. Oncolysis is restricted to cells with a dysregulated retinoblastoma protein pathway, which is frequently observed in MM. Further, LOAd viruses are armed with human immunostimulatory transgenes: trimerized membrane-bound CD40L (LOAd700, LOAd703) and 4-1BBL (LOAd703). LOAd viruses were assessed in a panel of MM cell lines (ANBL-6, L363, LP-1, OPM-2, RPMI-8226, and U266-84). All cells were sensitive to infection, leading to viral replication and cell killing as analyzed by quantitative PCR and viability assay. Transgene expression was verified post infection with flow cytometry. Cell phenotypes were further altered with a downregulation of markers connected to MM progression (ICAM-1, CD70, CXCL10, CCL2, and sIL-2Rα) and an upregulation of the death receptor Fas. In a co-culture of immune and MM cells, LOAd viruses promoted activation of cytotoxic T cells as seen by higher CD69, CD107a, and IFNγ expression. This was most prominent with LOAd703. In conclusion, LOAd viruses are of interest for MM therapy.

Naseri, SedighehUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)sadna643 (författare)
Hellström, Ann-CharlotteUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)annhe765 (författare)
Jernberg Wiklund, HelenaUppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi(Swepub:uu)helenajw (författare)
Eriksson, EmmaUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)emmsv898 (författare)
Loskog, Angelica S.,1973-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)angelosk (författare)
Uppsala universitetKlinisk immunologi (creator_code:org_t)

Ingår i:Cancer Gene Therapy: Springer Science and Business Media LLC27:12, s. 948-9590929-19031476-5500

Av författaren/redakt...: Wenthe, Jessica; Naseri, Sedigheh; Hellström, Ann-C ...; Jernberg Wiklund ...; Eriksson, Emma; Loskog, Angelica ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinsk biotek ...; och Medicinsk biotek ...

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