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Oncolytic vaccinia virus expressing a bispecific T-cell engager enhances immune responses in EpCAM positive solid

Min Wei1,2, Shuguang Zuo3, Zhimin Chen1

  • 1Affiliated Yancheng No.1 People's Hospital, Medical School of Nanjing University, Yancheng, China.

Frontiers in Immunology
|December 1, 2022
PubMed

Insights

A novel recombinant vaccinia virus encoding an EpCAM bispecific antibody (VV-EpCAM BiTE) effectively targets EpCAM-positive tumors. This approach enhances T-cell infiltration and activation, reducing tumor growth and boosting antitumor immunity.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunotherapy
  • Tumor microenvironment modulation

Background:

  • Cancer immunotherapy faces challenges due to insufficient T-cell infiltration and immune suppression within the tumor microenvironment (TME).
  • Effective strategies are needed to enhance tumor-specific immune surveillance and T-cell responses against solid tumors.

Purpose of the Study:

  • To investigate the therapeutic potential of a recombinant vaccinia virus encoding an EpCAM bispecific antibody (VV-EpCAM BiTE) for solid tumors.
  • To evaluate the ability of VV-EpCAM BiTE to modulate the TME and enhance antitumor immunity.

Main Methods:

  • Development and characterization of VV-EpCAM BiTE, a recombinant vaccinia virus expressing an EpCAM-targeting bispecific antibody.
  • In vitro assessment of viral infection, replication, cell lysis, and BiTE-mediated T-cell activation.
  • Intratumoral administration of VV-EpCAM BiTE in solid tumor models to evaluate antitumor activity and immune responses.

Main Results:

  • VV-EpCAM BiTE demonstrated effective viral replication and lysis of EpCAM-positive tumor cells.
  • Secreted EpCAM BiTE facilitated T-cell engagement with tumor cells, leading to T-cell activation and cytokine release (IFN-γ, IL-2).
  • Intratumoral VV-EpCAM BiTE treatment significantly enhanced antitumor activity, increased immune cell infiltration in the TME, reduced CD8+ T-cell exhaustion, and boosted T-cell-mediated immunity, particularly in tumors with high EpCAM expression.

Conclusions:

  • VV-EpCAM BiTE effectively combines oncolytic virotherapy and bispecific antibody functions to overcome TME-mediated immune suppression.
  • The study provides preclinical evidence supporting the therapeutic potential of VV-EpCAM BiTE for treating EpCAM-positive solid tumors.
Keywords:
EpCAMbispecific T-cell engagercancer therapysolid tumorvaccinia virus

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