Avid Bioservices Inc (CDMO)

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Another approach to understanding immune suppression vs. activation is to consider the specific interaction between exposed PS, M2 macrophages and bavituximab.

The specific cancer environment causes much PS to be exposed on the tumor cells and the associated vascular endothelial cells.

The regular day job of M2 macs is to calmly clean up any cell exposing PS. It may have been cancer caused, or just regular aging worn out cell replacement.

No immune activation takes place. This is a passive environment.

But when bavi is infused into the system something very different happens. Bavi covers the exposed PS, so only bavi is accessible to the M2 mac, and the M2 mac latches on to bavi instead.

Now the action begins!!

Instead of producing TGF-beta and IL-10, the M2 produces TNF-alpha and IL-12. Everything changes as the immune system goes into full activation mode, as can be seen in the cartoon below. We now have a proliferation of cytotoxic M1 macrophages, mature antigen presenting dendritic cells, and a variety of tumor specific cytotoxic T-cells.

The way to think about these processes is that through tumor induced PS exposure nothing much happens in the immune system. M2s eat cells with PS exposed, but send out no immune system alerts, and the tumor proliferates and grows larger. Think of it as a rather passive response.

On the contrary, bavi, through interaction with the M2 macrophage sets off alarm bells in the immune system. Everything goes into high gear from the PS checkpoint and bavi, through the macrophages, dendritic cells and the T-cells. Because of bavi, we have put the immune system on specific alert to the cancer. This is an active response.

So immune suppression is caused by the proliferation of exposed PS, and the M2 passive response. There is no “awareness” the the cancer danger.

When bavi is infused, and covers the exposed PS, the immune system is alerted to the cancer and develops a full and active immune response that destroys the tumor.

IMO

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