WHAT ARE IMMUNE THERAPIES?
Here’s a scary thought: everyday the immune system recognizes and kills tumor cells, making cancer a common occurrence—possibly as common as the flu virus— that is snuffed out before it has a chance to spread. At autopsy unsuspected tumors—unsuspected while the person was alive—are routinely discovered, which theoretically poses a problem for tissue and organ transplantation of skin, cartilage, heart valves and veins. Yikes! The clinical name for this monitoring process is immunosurveillance, which means that the immune system is on patrol, day and night, like a predatory police force that constantly scans the neighborhood—your own internal neighborhood—for signs of illegal activity that may signal cancer and then acts as judge, jury and potentially executioner of the cellular offenders. And thank goodness because without this zero tolerance policing the likelihood is that none of us would be here now to read these words. The survival of cancer cells critically depends on their ability to evade the immune system. And so it is that tumors, out of necessity, successfully manage to make the immune system turn a blind eye. How? By essentially subjecting the immune system to a restraining order.
As it turns out the T cells and B cells of immune system function through a complex series of checks and balances called checkpoints that prevent an abuse of power, which would result in autoimmune reactions, where the immune system indiscriminately attacks healthy tissues like in rheumatoid arthritis, sarcoidosis, psoriasis or lupus. Immune checkpoints like PD-1 and CTLA-4 control the balance of stimulatory and inhibitory activity of the immune system. Cancer cells, the successful cancer cells, at any rate, take advantage of these natural inhibitory checkpoint mechanisms and shift the delicate balance toward too little activity, in part, by binding to PD-1 and CTLA-4 and shutting down immunosurveillance.
The result: a see-no-evil, hear-no-evil immune system that is prevented from patrolling the “mean streets” of the lawless tumor, which grows wild and spreads to other parts of the body in the absence of immunosurveillance. A new class of anti-cancer therapies called checkpoint inhibitors, designed to reverse this situation by blocking the PD-1 and CTLA-4 receptors and preventing the cancer cells from binding to them, stimulates the T cells and B cells to do their job, attack the tumor and restore law and order. Hurray, right?
Well…not so fast. No question that PD-1 inhibitors like pembrolizumab (Keytruda) or nivolumab (Opdivo) and CTLA-4 inhibitors like ipilimumab (Yervoy) are game-changers but only in a percentage of patients (20-30%) and only in certain tumor types like melanoma, lung cancer and kidney cancer. This is a bad news/good news situation because the checkpoint inhibitors can be combined with other therapies to potentially make them more effective in patients and tumor types with poor response rates.
These therapies include epigenetic agents, like RRx-001, which turn beneficial immune genes back on that the tumor has silenced, radiation therapy and oncolytic viruses, like the VIMMUNE™ platform, both of which locally destroy cancer cells and lead to an increased immune presence in the vicinity of the tumor.
To borrow Winston Churchill’s famous quote in the context of cancer treatment with immune therapies, “Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”