Oncolytic therapy using a mutant type-1 herpes simplex virus and the role of the immune system

E S Lambright1, D J Caparrelli, A E Abbas

  • 1Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, USA.

Abstract

Insights

Herpes simplex virus (HSV)-1716 effectively prevented or suppressed Lewis lung carcinoma growth in mice. This oncolytic therapy shows promise for lung cancer treatment, even without immune system involvement.

Area of Science:

  • Oncolytic virotherapy
  • Cancer research
  • Immunology

Background:

  • Herpes simplex virus (HSV)-1716 is a replication-restricted HSV-1 with demonstrated efficacy against various cancers.
  • Previous studies highlight its potential in treating central nervous system tumors, breast cancer, ovarian cancer, and malignant mesothelioma.

Purpose of the Study:

  • To evaluate the efficacy of HSV-1716 as an oncolytic therapy in a murine model of lung cancer, specifically Lewis lung carcinoma.
  • To investigate the role of the immune system in HSV-1716's oncolytic activity.

Main Methods:

  • Lewis lung carcinoma cells were infected with HSV-1716 and implanted in mice at varying ratios of infected to uninfected cells.
  • Tumor burden was quantified by measuring tumor nodule weight.
  • Experiments were conducted in both immunocompetent and severe combined immunodeficient (SCID) mice to assess the immune system's role.
  • A vaccine effect was evaluated by implanting tumors on the opposite flank.

Main Results:

  • A 1:10 ratio of infected-to-uninfected cells completely prevented tumor formation in both immunocompetent and SCID mice.
  • A 1:100 ratio significantly suppressed tumor growth.
  • No significant difference in tumor size was observed in distant sites, indicating no vaccine effect.

Conclusions:

  • HSV-1716 demonstrates potential as an oncolytic therapy for lung cancer, independent of immune system induction.
  • The findings suggest that a "carrier" cell could be utilized to deliver HSV-1716 for therapeutic purposes.

Related Concept Videos

Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...