Top

Published in:

01-07-2014 | Translational Research and Biomarkers

Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma

Authors: Sergio A. Acuna, MD, Kathryn Ottolino-Perry, BSc, Besmira Çako, BSc, Nan Tang, MSc, Fernando A. Angarita, MD, J. Andrea McCart, MD, MSc, FRCS(C)

Published in: Annals of Surgical Oncology | Issue 7/2014

Abstract

Background

Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery.

Methods

Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy.

Results

The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed.

Conclusions

VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.

Mack TM. Sarcomas and other malignancies of soft tissue, retroperitoneum, peritoneum, pleura, heart, mediastinum, and spleen. Cancer. 1995;75(1 Suppl):211–44.PubMedCrossRef

Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005;366(9483):397–408.PubMedCrossRef

Manzini Vde P, Recchia L, Cafferata M, et al. Malignant peritoneal mesothelioma: a multicenter study on 81 cases. Ann Oncol. 2010;21(2):348–53.PubMedCrossRef

Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.PubMedCrossRef

Mirarabshahii P, Pillai K, Chua TC, Pourgholami MH, Morris DL. Diffuse malignant peritoneal mesothelioma: an update on treatment. Cancer Treat Rev. 2012;38(6):605–12.PubMedCrossRef

Sugarbaker PH. Managing the peritoneal surface component of gastrointestinal cancer. Part 2: perioperative intraperitoneal chemotherapy. Oncology (Williston Park). 2004;18(2):207–19; discussion 220-2, 227-8, 230.

Sugarbaker PH, Yan TD, Stuart OA, Yoo D. Comprehensive management of diffuse malignant peritoneal mesothelioma. Eur J Surg Oncol. 2006;32(6):686–91.PubMedCrossRef

Sugarbaker PH. Evolution of cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis: are there treatment alternatives? Am J Surg. 2011;201(2):157–9.PubMedCrossRef

Adusumilli PS, Stiles BM, Chan MK, et al. Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses. J Gene Med. 2006;8(5):603–15.PubMedCentralPubMedCrossRef

10.

Zhu ZB, Makhija SK, Lu B, et al. Targeting mesothelioma using an infectivity enhanced survivin-conditionally replicative adenoviruses. J Thorac Oncol. 2006;1(7):701–11.PubMedCentralPubMedCrossRef

11.

Kubo S, Kawasaki Y, Yamaoka N, et al. Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus. J Gene Med. 2010;12(8):681–92.PubMedCentralPubMed

12.

Willmon CL, Saloura V, Fridlender ZG, et al. Expression of IFN-beta enhances both efficacy and safety of oncolytic vesicular stomatitis virus for therapy of mesothelioma. Cancer Res. 2009;69(19):7713–20.PubMedCentralPubMedCrossRef

13.

Saloura V, Wang LC, Fridlender ZG, et al. Evaluation of an attenuated vesicular stomatitis virus vector expressing interferon-beta for use in malignant pleural mesothelioma: heterogeneity in interferon responsiveness defines potential efficacy. Hum Gene Ther. 2010;21(1):51–64.PubMedCentralPubMedCrossRef

14.

Silberhumer GR, Brader P, Wong J, et al. Genetically engineered oncolytic newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma. Mol Cancer Ther. 2010;9(10):2761–9.PubMedCentralPubMedCrossRef

15.

Gauvrit A, Brandler S, Sapede-Peroz C, Boisgerault N, Tangy F, Gregoire M. Measles virus induces oncolysis of mesothelioma cells and allows dendritic cells to cross-prime tumor-specific CD8 response. Cancer Res. 2008;68(12):4882–92.PubMedCrossRef

16.

Kelly KJ, Woo Y, Brader P, et al. Novel oncolytic agent GLV-1h68 is effective against malignant pleural mesothelioma. Hum Gene Ther. 2008;19(8):774–82.PubMedCentralPubMedCrossRef

17.

Zhang Q, Yu YA, Wang E, et al. Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus. Cancer Res. 2007;67(20):10038–46.PubMedCrossRef

18.

Breitbach CJ, Burke J, Jonker D, et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. 2011;477(7362):99–102.PubMedCrossRef

19.

Park BH, Hwang T, Liu TC, et al. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 2008;9(6):533–42.PubMedCrossRef

20.

Hwang TH, Moon A, Burke J, et al. A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma. Mol Ther. 2011;19(10):1913–22.PubMedCentralPubMedCrossRef

21.

McCart JA, Ward JM, Lee J, et al. Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res. 2001;61(24):8751–7.PubMed

22.

Davis MR, Manning LS, Whitaker D, Garlepp MJ, Robinson BW. Establishment of a murine model of malignant mesothelioma. Int J Cancer. 1992;52(6):881−6.PubMedCrossRef

23.

McCart JA, Mehta N, Scollard D, et al. Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: molecular imaging after systemic delivery using 111In-pentetreotide. Mol Ther. 2004;10(3):553–61.PubMedCrossRef

24.

Sugarbaker PH. Management of peritoneal-surface malignancy: the surgeon’s role. Langenbecks Arch Surg. 1999;384(6):576–87.PubMedCrossRef

25.

Jansen M, Treutner KH, Jansen PL, et al. Inhibition of gastric cancer cell adhesion in nude mice by inraperitoneal phospholipids. World J Surg. 2005;29(6):708–14.PubMedCrossRef

26.

Jarnagin WR, Zager JS, Klimstra D, et al. Neoadjuvant treatment of hepatic malignancy: an oncolytic herpes simplex virus expressing IL-12 effectively treats the parent tumor and protects against recurrence-after resection. Cancer Gene Ther. 2003;10(3):215–23.PubMedCrossRef

27.

Ebright MI, Zager JS, Malhotra S, et al. Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model. J Thorac Cardiovasc Surg. 2002;124(1):123–9.PubMedCrossRef

28.

Sugarbaker PH. Comprehensive management of peritoneal surface malignancy using cytoreductive surgery and perioperative intraperitoneal chemotherapy: The Washington Cancer Institute approach. Expert Opin Pharmacother. 2009;10(12):1965–77.PubMedCrossRef

29.

Bertino P, Panigada M, Soprana E, et al. Fowlpox-based survivin vaccination for malignant mesothelioma therapy. Int J Cancer. 2013;133(3):612–23.PubMedCrossRef

30.

Ho M, Feng M, Fisher RJ, Rader C, Pastan I. A novel high-affinity human monoclonal antibody to mesothelin. Int J Cancer. 2011;128(9):2020–30.PubMedCentralPubMedCrossRef

31.

Feng Y, Xiao X, Zhu Z, et al. A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity. Mol Cancer Ther. 2009;8(5):1113–8.PubMedCentralPubMedCrossRef

32.

Bridle BW, Stephenson KB, Boudreau JE, et al. Potentiating cancer immunotherapy using an oncolytic virus. Mol Ther. 2010;18(8):1430–9.PubMedCentralPubMedCrossRef

33.

Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, McCart JA. Intelligent design: combination therapy with oncolytic viruses. Mol Ther. 2010;18(2):251–63.PubMedCentralPubMedCrossRef

Title: Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma
Authors: Sergio A. Acuna, MD
Kathryn Ottolino-Perry, BSc
Besmira Çako, BSc
Nan Tang, MSc
Fernando A. Angarita, MD
J. Andrea McCart, MD, MSc, FRCS(C)
Publication date: 01-07-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue 7/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-014-3651-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2014

Laparoscopic-Assisted Versus Open Complete Mesocolic Excision and Central Vascular Ligation for Right-Sided Colon Cancer

Cost-Effectiveness of Contralateral Prophylactic Mastectomy for Prevention of Contralateral Breast Cancer

Androgen Receptor Expression Shows Distinctive Significance in ER Positive and Negative Breast Cancers

Prospective Study Evaluating Oncological Safety of Axillary Reverse Mapping

Prognosis After Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma Originating from Non-cirrhotic Liver

Pathology Review Significantly Affects Diagnosis and Treatment of Melanoma Patients: An Analysis of 5011 Patients Treated at a Melanoma Treatment Center