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Caprine herpes virus-1 reduces cell viability and enhances chemosensitivity in breast cancer cells
C A Iannuzzi1, F Pagano2, M Tomeo3
1Experimental Clinical Oncology of Breast Unit, Department of Breast and Thoracic Oncology, Istituto Nazionale Tumor IRCCS Fondazione G. Pascale (IRCCS) "Fondazione G. Pascale", Naples, Italy.
Introduction:
Oncolytic viruses (OVs) are promising therapeutic agents in oncology that directly lyse tumor cells, modulate the immune response, and alter the tumor microenvironment. Non-human OVs offer advantages over their human counterparts, such as being non-pathogenic in humans and lacking pre-existing immunity. In previous studies, we demonstrated that a non-human caprine herpesvirus 1 (CpHV-1) effectively kills various human cancer cell lines. In this study, we evaluate CpHV-1's antitumor effects across different breast cancer (BC) cell lines and its potential synergy with FDA-approved BC therapies.
Methods:
We assessed the effects of CpHV-1 on BC cell viability and clonogenic potential, cell cycle regulation, and apoptosis in MCF-7, T47D, SKBR3, and MDA-MB-468 cell lines, as well as in non-tumorigenic mammary epithelial cells (MCF-10A). Additionally, CpHV-1 was tested in combination with Abemaciclib, Tucatinib, and Inavolisib, and synergism was evaluated using Chou-Talalay analysis.
Results:
Our data show that CpHV-1 induced a dose-dependent cytotoxic effect, with an MOI of 5 reducing viability by ~50% 72 hours post-infection. Clonogenic assays confirmed long-term growth inhibition. We also demonstrated modulation of cell cycle progression and induction of apoptosis in tumor cells mediated by CpHV-1. Finally, combined treatments showed synergy across all BC subtypes, without significant toxicity in normal cells.
Discussion:
These findings highlight CpHV-1 as a promising oncolytic agent capable of targeting multiple breast cancer subtypes. Its ability to significantly reduce viability, impair long-term proliferation, and induce apoptosis, together with its synergistic activity when combined with FDA-approved targeted therapies and its limited toxicity in normal cells, supports further investigation of CpHV-1 for breast cancer treatment.
Insights
Caprine herpesvirus 1 (CpHV-1) effectively targets multiple breast cancer subtypes, reducing tumor cell viability and proliferation. This oncolytic virus shows synergistic effects with existing therapies and minimal toxicity to normal cells.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Virology
Background:
- Oncolytic viruses (OVs) are emerging cancer therapeutics.
- Non-human OVs offer advantages like reduced pre-existing immunity.
- Caprine herpesvirus 1 (CpHV-1) has shown prior efficacy against cancer cells.
Purpose of the Study:
- To evaluate CpHV-1's efficacy against diverse breast cancer (BC) cell lines.
- To assess CpHV-1's synergistic potential with FDA-approved BC therapies.
- To investigate CpHV-1's impact on BC cell cycle and apoptosis.
Main Methods:
- Assessed CpHV-1 effects on BC cell viability and clonogenic potential.
- Analyzed cell cycle regulation and apoptosis induction.
- Evaluated CpHV-1 in combination with Abemaciclib, Tucatinib, and Inavolisib using Chou-Talalay analysis.
Main Results:
- CpHV-1 demonstrated dose-dependent cytotoxicity, reducing viability by ~50% at MOI 5.
- Confirmed long-term growth inhibition via clonogenic assays.
- Showed modulation of cell cycle and induced apoptosis in tumor cells; synergistic effects observed with combination therapies without significant normal cell toxicity.
Conclusions:
- CpHV-1 is a potent oncolytic agent against multiple breast cancer subtypes.
- CpHV-1 exhibits significant antitumor effects and synergizes with targeted therapies.
- Limited toxicity in normal cells supports CpHV-1's potential for breast cancer treatment.
