Talimogene Laherparepvec: A groundbreaking viral therapy for late stage melanoma

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Classification

Baltimore classification: dsDNA
Family: Herpesviridae
Virion: Enveloped
Capsid symmetry: Icosahedral
Replication site: Nucleus and cytoplasm

Overview of Melanoma and effective treatment options

Overview of Melanoma and effective treatment options

Melanoma, one of the most dangerous forms of skin cancer, can occur when skin cells are exposed to UV radiation from the sun without protection [1]. When skin cells are frequently exposed to UV radiation, pigment producing cells called melanocytes can accumulate mutations within their DNA, and sometimes these mutations can cause them to turn cancerous [1]. Cancerous cells divide unchecked by normal cell signaling and multiply into tumors on the skin [1]. Melanoma can occur anywhere on the human epidermis including the head, neck, hips, back, and even the eye [2]. The reason melanoma is considered to be dangerous is that it frequently becomes metastatic, which means that it spreads to areas around the human body different from where it originated, and when cancer spreads it becomes extremely difficult to treat [2]. One of the most common ways to see if someone has melanoma is to check their body for moles. The moles are often discolored, change in size and shape over time, and are asymmetrical [2]. Melanoma can be staged in 5 different categories, 0-IV, with the earlier stages being the easiest to treat while the later stages are the most difficult to treat especially if the cancer has spread throughout the human body. In general, there are five different way of treating melanoma. The five most common techniques used are chemotherapy, surgery, immunotherapy, radiation therapy, and targeted therapy [2]. All of these treatments have positives and negatives associated with them, but this page will focus on one novel microbial based treatment for melanoma that falls within the immunotherapy category. One of the reasons to choose immunotherapy over other forms of treatment is that a variety of cancers can be treated because the immune system is being improved through the treatment [3]. Treatments such as radiation and chemotherapy are relatively ineffective against melanoma making immunotherapy one of the only viable options for patients with this illness [3]. Another benefit to immunotherapy is that its treatments have been shown to last longer in comparison to other therapies because the immune system is trained to recognize what cancer cells look like to eliminate them and inhibit tumor growth [3]. Immunotherapy is a more precise way to treat cancer than other common therapies such as chemo and radiation therapy which use radiation and toxic drugs that can be effective during treatment but cause extensive damage to normal human cells [3]. One of the most recent breakthroughs in immunotherapy was the development of the first Oncolytic virus called Talimogene Laherparepvec (T-VEC).



Figure 1: Transmission Electron Micrograph of a Herpes Simple Virus Particle by Jay C. Brown of the University of Virginia. [http://darwin.bio.uci.edu/~faculty/wagner/hsv2f.html.


Figure 2: Image of the local and systemic effects of T-VEC. The local impact of T-VEC includes replication within cancer cells and release of virus particles upon cell lysis. The systemic impact of T-VEC includes the release of tumor specific antigens and the activation of Dendritic cells by GM-CSF. [9][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519012/pdf/nihms709872.pdf
Figure 3: Image of the results from the Phase II and III T-VEC studies. The results shown include the number of patients, the stage of their melanoma, the objective response rates and overall survival. The objective response rates are a measure of the amount of patients who experienced a predetermined tumor size reduction. The durable response rates are a measurement of the length of patients response rates. Stage IIIc melanoma cannot be removed by surgery but remains localized to the original tumor. Stage IVa melanoma has begun to spread away from the original tumor, and stages IVb/c have spread to areas like the nervous and respiratory systems. [9] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519012/pdf/nihms709872.pdf


By Alex Fazioli



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Legend/credit: Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.
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Section 2

Include some current research, with at least one figure showing data.

Section 3

Include some current research, with at least one figure showing data.

Section 4

Conclusion

References


[1]Skin Cancer Foundation. Retrieved April 17, 2018, from https://www.skincancer.org/skin-cancer-information/melanoma

[2]Melanoma Treatment (PDQ®)-Patient Version. Retrieved April 18, 2018, from https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq

[3]Benefits of Cancer Immunotherapy. Retrieved April 24, 2018, from https://cancerresearch.org/immunotherapy/why-immunotherapy

[4] Dolgin, E. (2015). Oncolytic viruses get a boost with first FDA-approval recommendation. Nature Reviews Drug Discovery, 14(6), 369-371. doi:10.1038/nrd4643

[5] Pol, J., Kroemer, G., & Galluzzi, L. (2016). First oncolytic virus approved for melanoma immunotherapy. Oncoimmuneology, 5(1), e1115641 (3 pages)

[6]Liu, B. L., Robinson, M., Han, Z., Branston, R. H., English, C., Reay, P., & ... Coffin, R. S. (2003). ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Therapy, 10(4), 292.

[7] Hu, J. C., Coffin, R. S., Davis, C. J., Graham, N. J., Groves, N., Guest, P. J., ... & Medley, L. C. (2006). A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clinical cancer research, 12(22), 6737-6747.


[8] Senzer, N. N., Kaufman, H. L., Amatruda, T., Nemunaitis, M., Reid, T., Daniels, G., ... & Goldsweig, H. (2009). Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. Journal of Clinical Oncology, 27(34), 5763-5771.

[9] Korn, E. L., Liu, P. Y., Lee, S. J., Chapman, J. A. W., Niedzwiecki, D., Suman, V. J., ... & Parulekar, W. (2008). Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. Journal of Clinical Oncology, 26(4), 527-534.

[10] Johnson, D. B., Puzanov, I., & Kelley, M. C. (2015). Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. Immunotherapy, 7(6), 611-619.

[11] Puzanov, I., Milhem, M. M., Minor, D., Hamid, O., Li, A., Chen, L., ... & Kaufman, H. L. (2016). Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. Journal of Clinical Oncology, 34(22), 2619-2626.





Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2018, Kenyon College.