Exposed PS is a powerful immune system suppressant. When cancer occurs in the body, PS becomes specifically exposed on the surface of the tumor cells and the endothelial cells that line the vascular system which supplies nutrients to the tumors. When oncologists add irradiation or chemotherapy there is a further increase of the immunosuppressant, exposed PS, around the tumor environment. This increasing presence of immune suppressing PS allows the tumor to to thrive and grow without any strong immune response.
Bavi infuses into the patient’s system, and targets and covers the ubiquitous exposed PS. Even more PS targets are provided by chemo and radiation. With PS covered the immune system “sees” and responds to the presence of the “foreign” tumor. It’s then that the natural immune cascade of events begins.
Immunosuppressant M2 macrophages polarize to become cytotoxic M1 macrophages.
Dendritic cells mature and present multiple antigens to T-Cells which then become cytotoxic and also attack the tumor.
Every cell in the tumor environment that shows PS becomes a target for bavituximab to cover, thereby alerting and activating a full and natural immune attack on the tumor.
The same ubiquitous presence of exposed PS in the tumor environment, increased by chemo and radiation, and creating a multitude of targets for bavi, works against individual downstream immunotherapies like anti-PD1, anti-PDL1 or anti-CTLA4. The increasing presence of exposed PS further suppresses the immune system and allows the tumor to grow, largely unhindered. Anti-PD1, anti-PDL1 and anti-CTLA4 have comparatively limited targets which are, in fact, not even always readily present on all tumor cells, as is exposed PS.
Bavi is able to facilitate a global immune attack on cancers because of the universality of the PS target. Bavi tags the pervasive PS on cancer cells thereby allowing a full immune system attack on the tumors.
Downstream immunotherapies with more limited targets on cancer cells, will be able to target only tumor cells with their specific targets.
Dr. Brekken has stated that he thinks downstream immunotherapies may be used in combination therapy regimes with bavituximab, yielding 200% - 300% increased efficacy. That describes nothing less than immunotherapeutic synergy.
It may be, currently, that downstream immunotherapies are working in an adverse environment because of the immunosuppression allowed by the prevalence of exposed PS.
From the strength of Dr. Brekken’s statement alone, I expect that we will see future immunotherapy regimes in which bavi is combined with downstream immunotherapeutic mAbs, providing synergistic treatments for cancer and moving down the road toward long term maintenance and cures.
IMO
sunstar
