Chimeric Newcastle Disease Virus Vectors Expressing Human IFN-γ Mediate Target Immune Responses and Enable

Rofaida Mostafa Soliman1,2, Keisuke Nishioka1, Tomo Daidoji1

  • 1Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Biomedicines
|February 25, 2023
PubMed

Insights

Researchers developed new chimeric Newcastle disease viruses (NDVs) that evade existing immunity and show potential for repeated cancer treatment. These engineered NDVs can be used multiple times to enhance cancer therapy and immune cell interaction.

Area of Science:

  • Virology
  • Oncology
  • Immunology

Background:

  • Newcastle disease virus (NDV) shows promise as an oncolytic agent and vaccine vector.
  • Pre-existing immunity to NDV limits the efficacy of repeated administrations.
  • Novel strategies are needed to overcome immune escape for therapeutic applications.

Purpose of the Study:

  • To engineer recombinant chimeric NDVs with altered F and HN genes from APMV-2.
  • To enhance the immunogenicity and oncolytic potential of these chimeric NDVs.
  • To evaluate their ability to evade NDV antiserum and infect cancer cells.

Main Methods:

  • Generation of two chimeric NDVs (rNDV-2HN and rNDV-2F/2HN) by replacing NDV F and HN genes with APMV-2 genes.
  • Enhancement of immune response by inserting the human IFN-γ gene.
  • Assessment of virus neutralization by NDV antiserum and infection of cancer cell lines (HEp-2, respiratory, and colon).

Main Results:

  • The chimeric viruses exhibited significantly lower virus-neutralizing titers compared to wild-type NDV.
  • Both rNDV-2HN and rNDV-2F/2HN successfully escaped the neutralizing activity of NDV antiserum.
  • The chimeric viruses demonstrated infectivity against respiratory and colon cancer cell lines.

Conclusions:

  • Engineered chimeric NDVs can evade pre-existing NDV immunity.
  • These viruses hold potential as a repeatable therapeutic strategy for cancer treatment.
  • Enhanced chimeric NDVs can improve immune cell interaction in cancer therapy.