Bispecific VSV-G Engagers: A Platform for Cell-Type-Specific Delivery of Viral Vectors

A trimeric CEACAM8-based reversible engager blocks non-specific VSV infection via LDLR with an IC50 of 16.7 pM while enabling VSV-mediated lysis of CEACAM6-positive tumor cells.

• Why it matters: VSV-G-pseudotyped lentiviral vectors deliver efficiently ex vivo via LDLR but lack the cell-type specificity needed for in vivo gene therapy and tumor targeting.
• What they did: The authors engineered reversible engagers by fusing cell-specific ligands or antibodies to ~40-amino-acid VSV-G-binding domains of LDLR, then tested CEACAM8/CEACAM6 selectivity and anti-CD3 targeting in human PBMCs and NSG mice.
• The result: CEACAM8/CEACAM6 targeting selectively transduced CEACAM6-positive epithelial cells and supported tumor cell lysis, while anti-CD3 engagers selectively transduced non-preactivated T cells and enabled in vivo CAR T generation that sustained control of human OPM2 tumors in NSG mice.

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