in situ immunization: A new Path to personal immunotherapy

Scientists and physicians have known for decades that cancer can be recognized and controlled by the immune system. The process by which this occurs is commonly referred to as the "Cancer Immunity Cycle" (depicted above). Recent breakthroughs in cancer immunotherapy have come from agents that target immune inhibitory molecules called "immune checkpoints". Checkpoints facilitate immune evasion by tumors in the later steps of the cycle after T cell priming has occurred (later steps depicted in light green).  Recent evidence suggests that some patients that do not respond to immune checkpoint blockade have failed to mount a sufficient T cell response, primarily due to inadequate immune activation in the early steps of the cycle (depicted in light yellow). Therefore, development of new agents that are capable of activating the early steps of the Cancer Immunity Cycle are of high importance. Vaxiion believes VAX014 excels at this and provides a new path to more effective immunotherapy through in situ immunization.

In situ is a Latin term meaning "in its original place or position". In the field of cancer immunotherapy, in situ immunization is a treatment method that uses the patient's tumor itself as part of the therapy. Typically, this is achieved by direct injection of tumors (i.e. while they are in situ) with an immunostimulatory agent. Several different classes of immunostimulatory agents have been investigated in clinical trials and results from these studies have demonstrated in situ immunization can work, but also that the agents developed to date are suboptimal for one reason or another. Oncolytic viral-based therapies have been a category leader, but their activity is limited in tumor with intact antiviral genes and the timing of immunologic events within the early stages of the Cancer Immunity Cycle are not ideal.  And because they are potentially infectious, all virus-based agents require onerous biocontainment handling procedures that limit their clinical use.