Use of Oncolytic Viruses and Immunostimulation Therapy

For several years now, HSV-1 has been used in the biotechnology industry as a vector for transfection of eukaryotic cells and has also been used in different clinical trials. In 2007, researchers from London reported that they treated successfully (although modestly) a rare form of blindness caused by a mutation in a single gene (the gene encodes a protein that is important for producing pigments that absorb light in the eye). Most importantly, the patient did not suffer any side effects. More recently, researchers in France used a modified HSV-1 to introduce genes to correct a rare brain disorder (adrenoleukodystrophy) in two children.

Oncolytic viruses (VO) use cancer cells to replicate and selectively destroy altered tissue spreading within the tumor, without damaging normal tissue. In addition to this direct oncolytic activity, VOs are also very effective in inducing immune responses in infected tumor cells.

The VOs encompass a wide variety of DNA and RNA viruses that are selective for cancer or can be genetically modified. The VOs provide a diverse platform for immunotherapy; they act as vaccines in situ and can be armed with immune modulating transgenes or combined with other immunotherapies such as administration of Dendritic cells and Tumor Infiltrating Lymphocytes (TIL-NK)

Many of the characteristics of the neoplastic tissue provide a permissive environment for oncolytic viruses.

OVs have many features as an advantage in different therapeutic uses:

1.- Cancer cells cannot develop resistance to Oncolytic Viruses

2.- They replicate selectively in tumor cells are not pathogenic.

3.- There is a possibility that the dose of virus in the tumor increases over time.

4.- Safety features can be incorporated, such as drug sensitivity and immunity or Viral Neutralization mechanisms.

An important issue for therapy with Oncolytic Viruses is either systemic or local administration. With intravenous systemic administration multiple tumors can be attacked, however, intratumoral administration is more effective and the number of virions in the tumor tissue is increased in less time.

There have been numerous clinical trials of VO for cancer. As expected, most have been in phase I with some phase II trials. There is currently a phase III trial of an oncolytic HSV1 for melanoma (talimogene laherparepvec, T-Vec) of this Visur strain there is the final analysis showing results that will lead to the first approval by the US FDA. UU. From a VO for tumors.

Like many cancer vaccination strategies, our collaboration with the team of researchers from the National Institutes of Health has developed a type of OV that apart from generating lysis of cancer cells leaves an antigen in the survivors (for patenting ATC ) that can induce selective adaptive immune response in the body’s defense cells. The combination of the expression of ATC Known Tumor Antigens in the tumor and OV-mediated cell death induces enhanced migration and activation of T cells compared to infected tumor cells that only express viral antigens. This is coupled to a main vaccine strategy (which contains a VSH-1 blocking agent which limits the replication of the virus used.

The presence of HSV-1 has been detected worldwide. It is acquired mostly during childhood and lasts a lifetime. The vast majority of HSV-1 infections are cold sores (infections in the mouth or around them, so it is sometimes called cold sores, labial) without any vital commitment.

The viruses and their code were initially developed in plasmids to transfect bacterial cells and produce as many viruses as possible, subsequently tested with renal adenocarcinoma cell lines (769-p), squamous cell carcinoma (UPCI: SCC152) and corroborated that the virus replicated and generated lysis of cells cultured in vitro, we are currently carrying out tests with hepatocarcinoma and small cell lung carcinoma cell lines, to demonstrate their oncolytic activity.

Finally, we will evaluate the oncolytic activity in a murine model to be able to translate the technology to a phase 1 clinical study in humans, with this background our work group is in the task of innovating and developing new tools aimed at the well-being of our patients and the population with genetic predisposition to solid neoplasms.

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