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Using Herpes Viruses to Fight Cancer

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According to the National Center for Health Statistics, cancer is the second leading cause of death in the United States and is superseded only marginally by cardiovascular disease. As our population ages, it is possible that cancer may soon take over as the leading cause of death. It is therefore encouraging to note that treatment for numerous solid neoplasms has made great strides recently. Part of this trend involves the use of targeted immunotherapy; namely, the process of using one’s own immune system to attack tumors. This process has been shown to be successful in treating many cancers, including esophageal, ovarian, pancreatic, prostate and squamous cell carcinoma, among others.

A recent addition to immunotherapy uses a modified herpetic virus to target a specific type of cancer. This is accomplished, in part, by removing two specific genes from the virus. Removal of a neurovirulence gene prevents infection of the nervous system, while removing the second gene enhances tumor selectivity by deleting the ribonucleotide reductase expressing gene that controls DNA synthesis. Immunogenicity is further enhanced by adding genes to express immunostimulatory mediators or those that counteract T-cell exhaustion. Together, these enhancements allow the virus to target specific cancer cells while sparing normal tissue. Not only does this approach act on the primary neoplasm, it can also activate the patient’s immune system to attack similar tumors in other parts of the body.1

The herpes simplex virus (HSV-1) is a double-stranded neurotropic DNA virus and was the first oncolytic virotherapy vector. It was approved by the U.S. Food and Drug Administration (FDA) in 2015 for treating advanced cases of malignant melanoma under the generic name talimogene laherparepvec or TVEC. The virus replicates in tumor cells at the site of injection, causing them to burst. Secondary systemic circulation results in an innate immune cell activation and cytokine release, with subsequent specific T-cell activation and antitumor immune response. After therapy is complete, the virus can be inactivated with the use of the anti-herpetic drugs ganciclovir, acyclovir or valacyclovir.

A recent paper on the use of other HSV-1 based viruses reports promising results in a number of preclinical studies on combined tumor cell killing abilities and immunostimulation in a broad range of cancers. However, the authors point out that attempts at clinical applications have often been unsuccessful. It should be noted that safety in these trials has been good, even at the maximum achievable doses.2 The success of TVEC in treating melanoma that led to FDA approval has sparked renewed interest in this approach.

The challenge now is to come up with viruses that may be broadly applicable in more tumor types by engineering more potent viruses with enhanced tumor cell killing and immunogenic responses. Therapies using other HSVs have the potential to be efficient tools in anti-cancer treatment and may qualify as a potent partner in combination with chemotherapeutic, as well as immunotherapeutic, regimens.

Thomas G. Wilson Jr., DDS
Editor in Chief
[email protected]

 

References

  1. Aldrak N, Alsaab S, Algethami A, et al. Oncolytic herpes simplex virus-based therapies for cancer. Cells. 2021;10:1541.
  2. Koch MS, Lawler SE, Chiocca EA. HSV-1 oncolytic viruses from bench to bedside: An overview of current clinical trials. Cancers (Basel). 2020;12:3514.

From Decisions in Dentistry. January 2023;9(1)4.

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