Enhanced lentiviral gene delivery to mammalian cells via paired cell surface and viral envelope engineering.

Lentiviral vectors that facilitate gene delivery to desired cell types have been widely used in routine laboratory research and therapeutic cell engineering. However, the lack of proper entry receptors on many cell types often results in poor gene delivery. Here, we present a simple paired virus-cell engineering approach that promotes lentiviral gene delivery into mammalian cells.

Directed evolution-based discovery of ligands for in vivo restimulation of CAR-T cells.

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 elicits remarkable clinical efficacy in B-cell malignancies, but many patients relapse due to failed expansion and/or progressive loss of CAR-T cells. We recently reported a strategy to potently restimulate CAR-T cells in vivo, enhancing their functionality by administration of a vaccine-like stimulus comprised of surrogate peptide ligands for a CAR linked to a lymph node-targeting amphiphilic PEG-lipid (termed CAR-T-vax). Here, we demonstrate a general strategy to generate and optimize peptide mimotopes enabling CAR-T-vax generation for any CAR.