Combination Therapy of Oncolytic Newcastle Virus and Lenalidomide Enhanced Cytotoxicity in Prostate Cancer Cells

Authors
Mahdie Jafari 1
Shahriyar Abdoli 2
Majid Asgari 3
Masoud Moghaddam Pour 4
Mohammad Ali Shokrgozar 5
Zahra Sharifzadeh 1
1 Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
2 School of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran
3 Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran
4 Poultry Viral Vaccines Research and Production Department, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran
5 National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
10.61882/ibj.4367
Abstract
Background: Despite existing treatments, advanced solid tumors, such as prostate cancer (PCa), require the development of novel anticancer therapies. Oncolytic viruses (OVs) present a potential treatment option for solid tumors. Newcastle disease virus (NDV) is one of the most promising OVs that can replicate within and destroys human cancer cells. This study aimed to evaluate the cytotoxic and apoptotic effects of the NDV strain on human PCa cells in vitro. Additionally, We examined a novel treatment for PCa by combining Lenalidomide (Len) with NDV.

Methods: NDV strains La Sota, B1, and I2 were tested for cytotoxicity against several cell lines. A safety assessment was conducted in primary cells using peripheral blood mononuclear cells (PBMCs). Also, apoptosis induction was measured using annexin V/7AAD staining. Finally, the cytotoxic effects of NDV alone and in combination with Len, were assessed using MTT.

Results: The NDV showed cytotoxic effects on tumor cell lines and induced apoptosis in infected prostate cells compared to control cells. The NDV La Sota strain exhibited significant oncolytic capacity, reducing the viability of LNCaP and DU145 cells to less than 40% at specific concentrations, while showing no cytotoxic effects on primary PBMCs. Also, NDV induced apoptosis in the prostate cell line by 60%. Furthermore, Len enhanced the cytotoxicity of PCa cells when combined with NDV.

Conclusion: Our study confirms the efficacy of oncolytic NDV treatment for PCa, particularly utilizing the La Sota strain. When combined with Len, NDV indicates an enhanced effectiveness in destroying tumor cells. These findings suggest a prospective treatment approach that needs more preclinical and clinical studies to improve outcomes in PCa treatment.
Keywords
Oncolytic Newcastle virus
prostate cancer
Immunotherapy
combination therapy Lenalidomide