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Evaluation of the oncolytic potential of R2B Mukteshwar vaccine strain of Newcastle disease virus (NDV) in a colon cancer cell line (SW-620)

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Abstract

Virotherapy is emerging as an alternative treatment of cancer. Among the candidate oncolytic viruses (OVs), Newcastle disease virus (NDV) has emerged as a promising non-engineered OV. In the present communication, we explored the oncolytic potential of R2B Mukteshwar strain of NDV using SW-620 colon cancer cells. SW-620 cells were xenografted in nude mice and after evaluation of the safety profile, 1 x 107 plaque forming units (PFU) of NDV were inoculated as virotherapeutic agent via the intratumoral (I/T) and intravenous (I/V) route. Tumor growth inhibition was compared with their respective control groups by gross volume and histopathological evaluation. Antibody titer and virus survival were measured by hemagglutination inhibition (HI)/serum neutralization test (SNT) and real-time PCR, respectively. During the safety trial, the test strain did not produce any abnormal symptoms nor weight loss in BALB/c mice. Significant tumor lytic activity was evident when viruses were injected via the I/T route. There was a 43 and 57% tumor growth inhibition on absolute and relative tumor volume basis, respectively, compared with mock control. On the same basis, the I/V route treatment resulted in 40 and 16% of inhibition, respectively. Histopathological examination revealed that the virus caused apoptosis, followed by necrosis, but immune cell infiltration was not remarkable. The virus survived in 2/2 mice until day 10 and in 3/6 mice by day 19, with both routes of administration. Anti-NDV antibodies were generated at moderate level and the titer reached a maximum of 1:32 and 1:64 via the I/T and I/V routes, respectively. In conclusion, the test NDV strain was found to be safe and showed oncolytic activity against the SW-620 cell line in mice.

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Acknowledgements

The authors acknowledge Dr. Mukul Jain for granting permission for work in the Zydus Research Centre (ZRC); Dr. Krishnaroop for help with cell culture at ZRC, Ahmedabad; Dr.Gaurav M. Pandya, Dr.Ummed V. Ramani and Dr. Mamta Janmeda for carrying out real-time PCR work; the staff at ZRC, Ahemdabad, during the mice trial. We further acknowledge the funds and other support provided by Principal, Veterinary College and University Authorities, Navsari Agricultural University, Navsari, as well as ZRC, Ahmedabad.

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Authors and Affiliations

  1. Department of Veterinary Microbiology, College of Veterinary Science and Animal Husbandry, Navsari Agricultural University, Navsari, Gujarat, India

    Kishan K. Sharma, Irsadullakhan H. Kalyani & Dharmesh R. Patel

  2. Zydus Research Centre, Ahmedabad, Gujarat, India

    Jogeswar Mohapatra, Satish D. Patel, Abhijit Chatterjee, Dinesh R. Patel & Bhavesh Vyas

  3. Department of Veterinary Pathology, College of Veterinary Science and Animal Husbandry, Navsari Agricultural University, Navsari, Gujarat, India

    Priti D. Vihol

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  1. Kishan K. Sharma
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Correspondence to Kishan K. Sharma.

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Funding

This study was funded by the Government of Gujarat’s program entitled “Strengthening the Vanbandhu College of Veterinary Science and Animal Husbandry, Navsari phase–V” (Budget Head, 12404) and Zydus Research Centre, Ahmadabad.

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All authors declare that there lies no conflict of interest.

Ethical approval

All applicable guidelines were followed regarding housing, care and animal experimentation during the study. Necessary prior permission was obtained from institutional ethics committee of Vanbandhu College of Veterinary Science and animal husbandry, Navsari (No-013-VCN-VMC-2014) and Zydus Research Centre, Ahmadabad (No-ZRC/PH/BP/002/12-2K14) to carry out animal experiments.

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Sharma, K.K., Kalyani, I.H., Mohapatra, J. et al. Evaluation of the oncolytic potential of R2B Mukteshwar vaccine strain of Newcastle disease virus (NDV) in a colon cancer cell line (SW-620). Arch Virol 162, 2705–2713 (2017). https://doi.org/10.1007/s00705-017-3411-4

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