Targeted BiTE Expression by an Oncolytic Vector Augments Therapeutic Efficacy Against Solid Tumors

Clin Cancer Res. 2018 May 1;24(9):2128-2137. doi: 10.1158/1078-0432.CCR-17-2651. Epub 2018 Feb 6.


Purpose: Immunotherapy with bispecific T-cell engagers has achieved striking success against hematologic 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 antitumor immunity. In addition, we showed therapeutic efficacy of MV-BiTE in xenograft models of patient-derived primary colorectal carcinoma spheroids with transfer of peripheral blood mononuclear cells.Conclusions: 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. Clin Cancer Res; 24(9); 2128-37. ©2018 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression*
  • Humans
  • Immunotherapy
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / immunology*
  • Spheroids, Cellular
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Cancer Vaccines