Cancer vaccines are a class of immunotherapy drugs that hold much promise as a potentially curative treatment for cancer. However, historically attempts to harness the power of the immune system through vaccination to recognize and kill tumors, while demonstrating tantalizing effectiveness in animal models, has failed to translate to the clinic. The reasons for the failure of cancer vaccine drugs in the clinic is thought to be due to the ability of cancers to evoke mechanisms to evade immune destruction.
Research into the mechanisms by which tumors evade immune attack led to the discovery of checkpoint molecules. These are molecules expressed on the surface of tumor cells that send signals to killer immune cells that are present in the tumor beds. Killer immune cells are the effector cells capable of killing tumor cells. When a killer immune cell interacts with checkpoint molecules expressed on a tumor cell, signals are sent which turn off the killer cells and prevent an immune attack.
The purpose of checkpoint molecules is to prevent immune cell attack of normal cells. Without this mechanism there would be rampant autoimmune disease. Tumors use this natural immune suppressor mechanism to evade immune attack. Checkpoint blockade drugs are a new class of immunotherapy drugs. Several of these drugs have now been approved by the FDA, such as Yervoy, Opdivo and Keytruda. These drugs work by blocking the interaction of the checkpoint molecules on tumors and counter receptors on killer cells. In this manner, the tumors cannot turn off the killer cells. However, since checkpoint blockade drugs block checkpoint signals expressed universally on all cells in the body, their use in cancer is often associated with severe toxicities.
In addition, it is not enough to just block checkpoint molecules when attempting to mediate a killer immune cell attack against tumor cells. In order for checkpoint blockade to be effective, it is also necessary that there be killer immune cells resident in the tumor beds that are blocked by checkpoint signals. Most patients do not have resident killer immune cells in the tumor beds. This requirement for there to be resident killer immune cells and the rarity of having resident killer cells in tumor beds are reasons why the response rates of checkpoint blockade drugs are low. It is also why checkpoint blockade drugs were first approved in indications like melanoma where a higher percentage of patients have resident killer cells in the tumor beds than other indications.
Immunovative has developed the next generation of immunotherapy drugs using Mirror EffectTM technology which integrates cancer vaccine technology to create an effective killer cell response in the tumor beds of patients that did not develop such a response naturally with a mechanism to elicit a natural checkpoint blockade mechanism targeted only to the tumor and not to normal cells as occurs with current checkpoint blockade drugs.