Natural killer cell activated by attenuated newcastle disease virus (NDV) as anti-cancer therapy

TL;DR

This paper explores combining a weakened Newcastle Disease Virus with natural killer cells to improve cancer treatment by boosting immune response against breast cancer cells.

Contribution

The study demonstrates a novel combinatorial approach using attenuated NDV to enhance NK cell anti-tumor activity.

Findings

Combining attenuated NDV with NK cells significantly increased cytotoxicity against breast cancer cells.

NK cell adhesion and tumor cell surface disruption were observed with the combination treatment.

CD56 expression on NK cells was elevated, supporting enhanced functionality in treated groups.

Abstract

Natural Killer (NK) cells play a central role in innate immunity by targeting virally infected and malignant cells without prior sensitization. However, their activity is often suppressed within the tumor microenvironment. Oncolytic viruses such as Newcastle Disease Virus (NDV) not only selectively replicate in tumor cells but also stimulate immune responses, particularly NK cell activation. Combining attenuated NDV with NK cell therapy may therefore enhance anti-tumor efficacy.

This study aimed to investigate the synergistic anti-cancer potential of NK cells activated by attenuated NDV against breast cancer cell lines AMJ13 and MCF-7, with emphasis on cytotoxicity, adhesion, and immunophenotypic changes.

NK cells were isolated from peripheral blood using separation media and 8 µm mesh filtration, followed by expansion in culture with interleukin-15 (IL-15). Immunofluorescence assays were performed to characterize these NK cells by immunophenotyping through detection of CD3, CD16, Cd56 and CD57 expressions. Co-cytotoxicity was evaluated by WST assay in AMJ13 and MCF-7 cells exposed to NK cells, NDV, or the combination. NK adhesion to tumor cells was assessed by light microscope, scanning electron microscopy (SEM) and immunofluorescence by CD56 detection. Statistical analysis was conducted using GraphPad Prism, and combination effects were analyzed by CompuSyn software.

NK cells expanded effectively in IL-15–supplemented culture and displayed enhanced cytotoxicity when combined with NDV, leading to significantly reduced viability in both AMJ13 and MCF-7 cells compared with single treatments (p < 0.05). light and SEM analyses demonstrated NK cell adhesion, morphological alterations, and surface disruption of tumor cells. Immunofluorescence confirmed increased expression of NK marker (CD56) combination in treated groups, supporting functional enhance attachemtn of NK cells.

Attenuated NDV significantly augments NK cell-mediated cytotoxicity and adhesion against breast cancer cells. This combinatorial approach offers a promising immunotherapeutic strategy, highlighting the potential of integrating oncolytic virotherapy with NK cell-based therapy for cancer treatment.

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