HO-Inactivated RE88 Strain As a New Cancer Vaccine Carrier: Evaluation in a Mouse Model of Cancer

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2021 Jan 25

PMID 33488068

Citations 5

Authors

Yingzi Fan

Tingting Bai

Yaomei Tian

Bailing Zhou

Yuanda Wang

Li Yang

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aimed to describe a novel cancer vaccine developed using HO-inactivated RE88 [with deletions of AroA (the first enzyme in the aromatic amino acid biosynthesis pathway) and DNA adenine methylase] as the carrier.

Methods: The pVLT33 plasmid was used to engineer an RE88 strain induced to express ovalbumin (OVA) by isopropylthiogalactoside (RE88-pVLT33-OVA). The immune responses and anticancer effects of HO-inactivated RE88-pVLT33-OVA were compared with those of non-inactivated RE88-pVLT33-OVA and OVA (positive control) in mice carrying OVA-expressing tumors (EG7-OVA) cells.

Results: Anti-ovalbumin IgG (immunoglobulin G) titer following vaccination with HO-inactivated RE88-pVLT33-OVA was higher for subcutaneous than for intragastric vaccination. When subcutaneous administration was used, HO-inactivated RE88-pVLT33-OVA (2 × 10 CFU (colony forming units)/mouse) achieved an anti-ovalbumin IgG titer higher than that for the same dose of RE88-pVLT33-OVA and comparable to that for 10 µg ovalbumin (positive control). The binding of mouse serum antibodies to EG7-OVA cells was stronger for HO-inactivated RE88-pVLT33-OVA (2 × 10 CFU/mouse) than for 10 µg ovalbumin. Furthermore, subcutaneous vaccination with HO-inactivated RE88-pVLT33-OVA (2 × 10 CFU/mouse) induced greater activation of splenic T cells and more extensive tumor infiltration with CD4/CD8 T cells compared with 10 µg ovalbumin (positive control). The mice vaccinated subcutaneously with HO-inactivated RE88-pVLT33-OVA at a dose of 2 × 10 or 6 × 10 CFU/mouse had smaller tumors compared with mice in the negative control groups. Tumor weight in mice vaccinated with HO-inactivated RE88-pVLT33-OVA at a dose of 2 × 10 CFU/mouse was significantly lower than that in both negative control groups ( < 0.05) and decreased with the increasing dose of HO-inactivated RE88-pVLT33-OVA. HO-inactivated RE88-pVLT33-OVA was potentially safer than the non-inactivated strain, could carry exogenous antigens, and had specific epitopes that could be exploited as natural adjuvants to facilitate the induction of cellular and humoral immune responses.

Conclusion: It was anticipated that HO-inactivated RE88-pVLT33-OVA could be used as a novel delivery system for new cancer vaccines.

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