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Speck, Tobias [VerfasserIn]; Heidbüchel, Johannes P. W. [VerfasserIn]; Veinalde, Rūta [VerfasserIn]; Jäger, Dirk [VerfasserIn]; Kalle, Christof von [VerfasserIn]; Ball, Claudia R. [VerfasserIn]; Ungerechts, Guy [VerfasserIn]; Engeland, Christine Elisabeth [VerfasserIn]

Targeted BiTE expression by an oncolytic vector augments therapeutic efficacy against solid tumors

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  • Medientyp: E-Artikel
  • Titel: Targeted BiTE expression by an oncolytic vector augments therapeutic efficacy against solid tumors
  • Beteiligte: Speck, Tobias [VerfasserIn]; Heidbüchel, Johannes P. W. [VerfasserIn]; Veinalde, Rūta [VerfasserIn]; Jäger, Dirk [VerfasserIn]; Kalle, Christof von [VerfasserIn]; Ball, Claudia R. [VerfasserIn]; Ungerechts, Guy [VerfasserIn]; Engeland, Christine Elisabeth [VerfasserIn]
  • Erschienen: February 6, 2018
  • Erschienen in: Clinical cancer research ; 24(2018), 18, Seite 2128-2137
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.CCR-17-2651
  • ISSN: 1557-3265
  • Identifikator:
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: PURPOSE: Immunotherapy with bispecific T cell engagers has achieved striking success against hematological malignancies, but efficacy against solid tumors has been limited. We hypothesized that oncolytic measles viruses encoding bispecific T cell engagers (MV-BiTEs) represent a safe and effective treatment against solid tumors through local BiTE expression, direct tumor cell lysis and in situ tumor vaccination. EXPERIMENTAL DESIGN: To test this hypothesis, we generated MV-BiTEs from the Edmonston B vaccine strain to target two model antigens. Replicative and oncolytic potential were assessed by infection and cell viability assays, respectively. Functionality of virus-derived BiTEs was tested in vitro by complementary binding and cytotoxicity assays. In vivo efficacy of MV-BiTE was investigated using both syngeneic and xenograft mouse models of solid cancers. RESULTS: We verified secretion of functional BiTE antibodies by MV-BiTE-infected cells. Further, we demonstrated therapeutic efficacy of MV-BiTE against established tumors in fully immunocompetent mice. MV-BiTE efficacy was associated with increased intratumoral T cell infiltration and induction of protective anti-tumor immunity. Additionally, we showed therapeutic efficacy of MV-BiTE in xenograft models of patient-derived primary colorectal carcinoma spheroids with transfer of PBMCs. CONCLUSION: MV-BiTE treatment was effective in two distinct models of solid tumors without signs of toxicity. This provides strong evidence for therapeutic benefits of tumor-targeted BiTE expression by oncolytic MV. Thus, this study represents proof of concept for an effective strategy to treat solid tumors with BiTEs.
  • Zugangsstatus: Freier Zugang