Written by Chrystal Moulton, Staff Writer. Treatment of malignant pleural mesothelioma with genetically engineered virus improves survival time by 18 months in Phase 1 trial.
In a case study of a 68-year old male with malignant pleural mesothelioma (1), researchers saw very encouraging results. The patient was treated previously with two rounds of chemotherapy (cisplatin/pemetrexed and docetaxel alone) along with radiotherapy. However, the cancer continued to progress despite those therapies. The patient then opted to participate in a Phase I trial of a genetically engineered virus (adenovirus labeled ONCOS-102) equipped with a granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically made to promote tumor cell death and boost immune system response to the tumor by recruiting antigen presenting cells (a specific type of immune white blood cells) and natural killer white blood cells to the tumor site.
The virus was injected into the tumor on 4 occasions (day 1, 4, 8, and 15) while researchers examined the patient carefully for any side effects of treatment. Researchers repeated dosing in order to ensure viral replication within the tumor cells followed by the subsequent destruction of the tumor cells. To further increase the therapeutic effect, the patient was also given intra-tumoral injections on days 29, 57, 85, 113, and 141. Cyclophosphamide, a common drug used in cancer treatment was also prescribed during the time of treatment for its immune-suppressing properties.
A biopsy taken 29 days after treatment revealed a more than 100-fold increase in tumor infiltrating white blood cells (called the CD8+ T-cells) compared to baseline. Previous research in cancer treatment has found a positive correlation between pretreatment counts of tumor infiltrating white blood cells (specifically CD8+ T-cells) and good clinical outcome. (2) The biopsy indicated that treatment with the ONCOS-102 adenovirus construct stimulated a strong tumor infiltrating cell response. Researchers also confirmed that the treatment induced a tumor specific immune response rather than an antiviral response. The treatment was also associated with an increase in genetic expression of typical immune defense proteins including interferon-gamma and other Th1 associated chemokines. Furthermore, during the follow-up period 7.5 months after treatment, researchers observed a 47 % decrease in metabolic activity within the tumor compared to 6 months after treatment further confirming tumor cell death. No further treatment was given to the patient after the trial period (141 days). The patient survived for 18 months from the beginning of the experimental adenovirus construct treatment. Total survival from the time of diagnosis was almost 3 years. Median survival for patients with malignant pleural mesothelioma is 4-12 months from diagnosis.
Overall, in a single experimental patient case, intra-tumoral injections with the ONCOS-102 adenovirus construct (an adenovirus specifically made to induce anti-tumor effects) demonstrated an increase in anti-tumor immunity and expression of proteins required in immune defense. Side effects noted from the treatment were generally mild with the exception of a fever. Researchers believe the results from this case study could suggest the use of the ONCOS-102 adenovirus construct in conjunction with other immunotherapies to fight cancer.
Source: Tuuli Ranki, Timo Joensuu, Elke Jäger, Julia Karbach, Claudia Wahle, Kalevi Kairemo, Tuomo Alanko, Kaarina Partanen, Riku Turkki, Nina Linder, Johan Lundin, Ari Ristimäki, Matti Kankainen, Akseli Hemminki, Charlotta Backman, Kasper Dienel, Mikael von Euler, Elina Haavisto, Tiina Hakonen, Juuso Juhila, Magnus Jaderberg, Petri Priha, Lotta Vassilev, Antti Vuolanto & Sari Pesonen (2014) Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8+ T-cell response, prominent infiltration of CD8+ lymphocytes and Th1 type polarization,OncoImmunology, 3:10, e958937, DOI: 10.4161/21624011.2014.958937
To link to this article: http://dx.doi.org/10.4161/21624011.2014.958937
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Posted August 18, 2015.
N.B. Prescription drugs can save lives but may also cause unwanted side effects. Thus not all drugs are considered safe. Consult with your medical healthcare provider for more information on a specific drug of interest.
Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.
References:
- Ranki T, et al. Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8+ T-cell response, prominent infiltration of CD8+ lymphocytes and Th1 type polarization. Oncoimmunology. 2014 Dec 15;3(10):e958937.
- Yamada N, et al. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol Immunother. 2010 Oct;59(10):1543-9.
