Oncolytic Virotherapy in Treating Advanced Melanoma

Summary

Melanoma is a skin cancer caused by UV radiation lysing melanocytes’ DNA under the epidermis. It can also be caused by an existing mole or pigmented skin growth. Common symptoms are a noticeably different spot on the skin, persistent itching, bleeding or crusting of a pigmented lesion, while metastatic spread may induce headaches, vision changes, hemoptysis, shortness of breath, dyspnea, seizures, changes in bowel habits, new-onset back pain, fevers, chills, night sweats, weight loss, etc. Melanoma is most common in fair skinned people, since the minimal amounts of melanin they produce won’t reflect uv radiation as well as a dark skinned person. Melanoma occurs easily when KRAS, HRAS, RB1, and MAP2K1 genes are mutated.

Oncolytic Virotherapy is when viruses are used to kill tumor cells. Viruses are genetically engineered to attach only to tumor cells through a surface protein and then enter and lyse the tumor cell. There is another failsafe in the virus that was genetically engineered by Crispr-Cas-9 to stop the virus from killing regular cells. It is not able to replicate in regular and immune cells, so it will die, but the virus can replicate in tumor cells so it will lyse the cell. The virulence genes are also removed to ensure safety of the normal cells. With no virulence gene the virus is physically incapable of causing normal infections. Another gene used is the Human gene GM-CSF, which is added to attract white blood cells to fight the cancer cells. They also use local injection to be able to have a targeted area for the oncolytic virotherapy.

Oncolytic Virotherapy can be used on more cancers than melanoma, but it is most effective with cancers that resist conventional therapies. Also Oncolytic Virotherapy needs a local injection which is why the only FDA approved oncolytic virotherapy, called Tailmogene laherpavec (T-VEC), is a treatment for Melanoma. T-VEC is a downgraded herpes virus which was discovered naturally by mutations.Some problems are it is pretty expensive to genetically engineer viruses, direct injection is difficult for metastatic spread, pre-existing immune cells can kill the viruses and you might need to take multiple therapies to counter advanced cancers past metastatic spread. On the other hand some benefits are that it will kill cancer cells with targeted cell lysis and tumor cell destruction causes an immune response.

This is a diagram of how Oncolytic Viruses go into cancer cells through viral infection and lyse them by reproducing while when a cancer cell infects an immune cell or a normal cell, the virus cannot duplicate and will die.
(Figure representation created by the author: Sahil Mehta)

Impact Statement

Sahil Mehta

"

I learned many things incorperating not just information but life skills I will be able to use in the future. I have learned how to make a good scientific poster and organize my research into a formal and well researched poster. I understand hwere and how I need to get my information and what type of information should be prioritized and used in a research project.

Student Reflection

By: Sahil Mehta.
The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of ELIO Academy.