Combinatorial leaky probiotic for anticancer immunopotentiation and tumor eradication.

ABSTRACT: Combination therapies present a compelling therapeutic regimen against the immunosuppressive and heterogeneous microenvironment of solid tumors. However, incorporating separate therapeutic modalities in regimen designs can be encumbered by complex logistical, manufacturing, and pharmacokinetic considerations. Herein, we demonstrate a single-vector combinational anticancer therapy using an lpp gene knockout leaky probiotic for simultaneous secretion of immunotherapeutic and oncolytic effector molecules. Through fusion protein design and vector optimization, a Nissle1917 (EcN) bacteria vector is engineered to secrete Neoleukin-2/15 (Neo-2/15) cytokine-functionalized anti-PDL1 nanobody (aPDL1-Neo2/15) and anti-mesothelin-functionalized hemolysin E (HlyE-aMSLN). The multifunctional leaky probi

SUBMITTER: Liu CH 

PROVIDER: S-EPMC11604515 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature