Oncolytics Biotech Inc ONCY

Breast cancer treatment: perspectives on the oncolytic virus

[Noteable]

Here is a new review appearing in "Frontiers" on oncolytic virus, including reovirus, in the treatment of breast cancer suggesting that multi-approach strategies - combining OVs and chemotherapy, radiotherapy, or immunotherapy - provide better therapeutic effects and show great potential in future approaches to breast cancer treatment.

March 20, 2024 - "Reovirus is a double-stranded RNA virus. Its replication is promoted in cells with an activated RAS pathway. The gain-of-function mutations, activating RAS signalling, are prevalent in cancers. Therefore, reovirus is a natural candidate for a therapeutic agent (45). Reovirus has oncolytic activity in vitro against multiple solid tumour types, including breast cancer (46). Reolysin is an unmodified wild- type oncolytic reovirus. In 2017, it received FDA approval for the treatment of metastatic breast cancer (46). Data from the Phase II trial for the treatment of advanced metastatic breast cancer showed that the combination of Reolysin and Paclitaxel significantly increased overall survival for about seven months (47). Clinical studies have demonstrated its effectiveness in combination with systemic anti-programmed cell death protein 1 (PD-1). In a murine breast cancer model, intratumoral reovirus increased PD-L1 expression on tumour cells, and combination reovirus/anti-PD-1 treatment improved survival by reducing Treg numbers and ameliorating tumour-specific cytotoxic T lymphocyte responses (48). Reovirus has also been used in combination with CD3-bispecific antibodies. Reovirus-induced IFN stimulated the recruitment of NK cells and reovirus-specific CD8+ T cells to the tumour site, while reovirus-specific effector T cells acted synergistically with CD3- bispecific antibodies, reducing the in vivo growth of several tumour types, including breast (46). Interestingly, this combination treatment was also effective against distant lesions that were not previously injected with reovirus. It suggests the possibility of using this therapy in case of metastatic disease (45). The advances in reovirus engineering have enabled the creation of oncolytic reoviruses that can antagonize inhibitory mechanisms within the TME. In particular, mutations in viral cell attachment protein σ1 gene, have been incorporated to prevent proteolytic cleavage and inactivation of σ1 by breast cancer-associated proteases". 

The advent of precision medicine calls for tailoring OVs to individual patient profiles. Developing personalised viral platforms could involve genetic modifications or viral engineering to enhance tumour specificity, replication efficiency, and immune activation while mitigating adverse effects. Advancements in identifying predictive biomarkers for treatment response remain also urgent. Identifying biomarkers associated with the efficacy of OVs can aid in patient stratification, ensuring targeted therapies for individuals most likely to benefit. 

An exciting frontier remains the synergy between OVs and conventional treatments like chemotherapy, radiotherapy, and immunotherapy. Exploring combination therapies can capitalize on their complementary mechanisms, potentially amplifying therapeutic efficacy and overcoming resistance. 

It is also crucial to find strategies that restore the tumour microenvironment and bolster anti- tumour immune responses. This includes interventions that regulate immune checkpoints, modulate cytokine profiles, or stimulate adaptive immune cells within the tumour milieu.

 

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1375433/full