Herpes Simplex virus for biological drugs against cancer

Herpes simplex virus can be used to generate biological drugs with oncolytic activity on HER2-negative breast cancers, of which so-called triple-negative breast cancers (TNBCs) are also a part.

This is what has been revealed by the studies that researchers at CEINGE-Advanced Biotechnology of Naples and the Department of Molecular Medicine and Medical Biotechnology of the Federico II University, led by Nicola Zambrano, professor of Molecular Biology, who in the laboratories of the Center in via Gaetano Salvatore has been working on the development of precisely new technologies for the selection and production of biological drugs for preclinical trials, havebeen carrying out for about five years now.

The scientists have generated, in collaboration with NousCom SRL, a herpes virus capable of selectively infecting cancer cells that expose, on their surface, mesothelin, a tumor antigen frequently expressed in TNBC tumors and pleural mesothelioma.

"Herpes simplex belongs to a family of viruses with which humans have always coexisted," Prof. Zambrano points out, "just think of the common labial manifestations that affect so many of us, and it is very well known. Against this virus there are also drugs to control its infection. These characteristics have made it a model of choice for the development of biological drugs with antitumor or, more precisely, oncolytic activity.

"The advantages of the viral vectors we generated, validated by experimentation on cells and in preclinical models," Zambrano explains, "lie in the correct balance of efficacy in activating the anti-tumor immune response and oncolytic specificity toward the tumor, with limitation of off-target effects toward normal tissues. Our studies envisage the use of these viral vectors in combination with tumor immunotherapy, which is increasingly emerging as the fourth presidium for anti-cancer treatments, in addition to more invasive therapies such as chemotherapy, radiotherapy and surgery."

This virus joins those generated in collaboration with the University of Bologna for targeting HER2-positive breast cancer, effectively expanding the potential therapeutic "arsenal" against breast and nonbreast cancers.

In addition to "educating" the viruses to make them effective and selective, the CEINGE laboratory directed by Prof. Zambrano represents a veritable training ground for numerous Biotechnology students and doctoral students, who have the opportunity to train themselves, both theoretically and practically, in the use of innovative molecular research methodologies and approaches, especially for cancer treatment.

"For the past five years we have been carrying out studies to educate Herpes simplex to selectively recognize cancer cells, and to replicate exclusively in them, leaving out normal cells. The initial model was based on recognition of HER2-positive breast tumors, and we improved it in selectivity toward the tumor. We then generated a new virus that could also recognize HER2-negative mammary tumors through a different receptor, mesothelin. This receptor could also be exploited for entry of the new oncolytic virus into mesothelioma cells, a particularly aggressive tumor with limited therapeutic options."

The results of the studies have been the subject of a series of very recent publications, the most recent in January 2021, the least recent in March 2020. The research activity has benefited from SATIN funding from the Campania Region, although the analysis of some of the mechanisms of antiviral immunity is also of interest for the elucidation of the pathogenetic mechanisms in charge of Covid-19 and which, therefore, also report the Campania Region's contribution to the CEINGE Covid-19 Task-Force.

The research group led by Nicola Zambrano, also formed by young researchers such as Guendalina Froechlich (SEMM doctoral student) and Chiara Gentile (DMMBM doctoral student), was joined by Dr. Emanuele Sasso of NousCom Srl, Alfredo Nicosia, professor of molecular biology at the Federico II University and CEINGE Principal Investigator, and the group of Massimo Mallardo, professor of cell biology at the Federico II University.