New Pathways for Oncolytic Virals in Breast Cancer

Johanna Kaufmann, PhD, executive vice president of oncology and immunology at Codagenix, summarizes an abstract she presented at the Society for Immunotherapy of Cancer Annual Meeting 2023 held November 1-5, 2023.

Here, Kaufmann discusses CodaLytic, the first codon-modified virotherapy candidate intended to stimulate an anti-tumor response in breast cancer.

Transcription:

0:09 | So at SITC, we provided an update on the mechanism of action of the first codon-modified virotherapy that we are developing at Codagenix. Virotherapy commonly is referred to also as oncolytic viral therapy. This particular virus that we're characterizing here, it's called CodaLytic. It is a codon-modified influenza virus that is synthetically engineered using the platform technology that is proprietary to Codagenix.

0:37 | We had previously shown in a selected set of breast cancer preclinical models that this virus can slow down tumor growth in some models, also cure tumors in animals, and engage a variety of immune mechanisms that you would associate with supporting of effector immune function. And the data we provided at SITC now expands that to a whole set of preclinical mouse models that are all immune competent and allow you to test these mechanisms of action. Specifically, we focused on the immune cells and the types of immune cells that are being recruited to the tumor upon treatment, either using CodaLytic alone or in combination with a variety of known anti-tumor agents, including checkpoint inhibitors. And what is consistent across all these different models is that we recruit T cells, specifically granzyme B cytotoxic CD8 T cells, to the tumor and increase their frequency.

1:53 | In addition, we recruit a certain subtype of dendritic cell to the tumor that is known at being very good for cross-presentation and presenting tumor antigen. And both of these cell types highly, significantly correlate directly in their amount with the reduction in tumor growth that you can see in the treated animal. And that obviously suggests that the virus works in the intended fashion that it creates an repurposed tumor microenvironment that allows anti-tumor immune function.

2:27 | I think what is specifically unique to this virus is the engineering platform that goes behind it. The the basis about viral engineering or selection of species that you need to consider is the fact that you need to make these viruses somehow specific for the tumor, while leaving healthy cells alone in order to make the safe administration in humans ultimately. And in order to create this tumor specificity for many viral species, you end up deleting certain genes or chunks of certain genes in order to create a phenotype that that allows this virus to be safely administered. But at the same time, you'll often then reduce either the sort of potency of the virus in tumor cells and or you remove components of the virus that are otherwise immune-stimulatory.

3:22 | Therefore, then many other oncolytic viruses need to overcome that in some way by inserting transgenes or some other technology. Our virus engineering platform that is the foundation of Codagenix essentially avoids having to delete entire sections of the viral genome. We attenuate our virus in the context of healthy cells by utilizing the redundancy in the genetic code. So you know that multiple, many, most actually, amino acids can be encoded by multiple codons, and viruses evolve to use optimal codons for efficient replication, which ultimately might cause disease in their respective host. We exchange codons and introduce silent mutations into selected parts of viral genomes that slows down translation of those proteins and therefore reduces viral replication in healthy cells. However, tumor cells that have defects in viral sensing pathways as well as cell death resistance mechanisms that are activated as part of malignant transformation. These mechanisms allow the virus to replicate more freely. And that is one layer of tumor specificity that we achieved through this engineering platform.