NDV-GT wth hyperacute rejection in cancer therapy

TL;DR

NDV-GT is a modified virus that triggers a strong immune response against tumors, showing high effectiveness in early clinical trials.

Contribution

NDV-GT uses α-Gal epitopes to induce hyperacute rejection and reprogram the tumor microenvironment, offering a novel oncolytic therapy.

Findings

NDV-GT triggers hyperacute rejection via α-Gal epitopes and natural antibodies.

NDV-GT converts 'cold' tumors into 'hot' ones by enhancing T-cell infiltration and cytokine secretion.

NDV-GT inhibits PI3K/AKT and NF-κB pathways, promoting tumor cell apoptosis.

Abstract

•NDV-GT expresses α-Gal epitopes on tumor cells to trigger hyperacute rejection.•NDV-GT reprograms the TME, enhancing T-cell infiltration and cytokine secretion.•Preliminary clinical data show 90.0 % disease control rate with no severe adverse events.•NDV-GT inhibits PI3K/AKT and NF-κB pathways, promoting apoptosis and tumor regression.•CRISPR-engineered macaque HCC model validates translational potential of NDV-GT.

NDV-GT expresses α-Gal epitopes on tumor cells to trigger hyperacute rejection.

NDV-GT reprograms the TME, enhancing T-cell infiltration and cytokine secretion.

Preliminary clinical data show 90.0 % disease control rate with no severe adverse events.

NDV-GT inhibits PI3K/AKT and NF-κB pathways, promoting apoptosis and tumor regression.

CRISPR-engineered macaque HCC model validates translational potential of NDV-GT.

Oncolytic viruses (OVs) represent a promising immunotherapy for cancer treatment, though their clinical application is often limited by systemic toxicity and low immunogenicity. To address this, we developed NDV-GT, a genetically engineered Newcastle disease virus that encodes porcine α-1,3-galactosyltransferase. These epitopes are recognized by pre-existing natural antibodies, triggering a hyperacute rejection response characterized by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Furthermore, NDV-GT modulates the tumor microenvironment by promoting T-cell infiltration and cytokine secretion, converting immunologically “cold” tumors into “hot” ones. Mechanistically, the virus inhibits PI3K/AKT and NF-κB signaling pathways, inducing apoptosis and suppressing tumor proliferation. In a preliminary clinical study of 20 patients with advanced refractory carcinomas, NDV-GT achieved a 90.0% disease control rate with no serious adverse events, underscoring its potential as a novel, safe, and effective oncolytic agent that elicits robust antitumor immunity.

Figures