Checkpoint Inhibitors (Theory & Praxis)

Checkpoint inhibitors seek to overcome one of cancer’s main defenses against an immune system attack. (1) Immune system T cells patrol the body constantly for signs of disease or infection. When they encounter another cell, they probe certain proteins on its surface, which serve as insignia of the cell’s identity. If the proteins indicate the cell is normal and healthy, the T cell leaves it alone. If the proteins suggest the cell is infected or cancerous, the T cell will lead an attack against it.

Once T cells initiate an attack, the immune system increases a series of additional molecules to prevent the attack from damaging normal tissues in the body. These molecules are known as immune checkpoints.

Tumor cells often wear proteins that reveal the cells’ cancerous nature. But they sometimes commit what amounts to identity theft, arraying themselves in proteins of normal cells. Recent research has shown that cancer cells often utilize immune checkpoint molecules to suppress and evade an immune system attack. T cells, deceived by these normal-looking proteins, may allow the tumor cell to go unmolested.

Checkpoint inhibitors block these normal proteins on cancer cells, or the proteins on T cells that respond to them. The result is to remove the blinders that prevented T cells from recognizing the cells as cancerous and leading an immune system assault on them.

Discussion & Limitations

Three checkpoint inhibitors have received rapid approval from the U.S. Food and Drug Administration for cancer, including ipilimumab (Yervoy®), pembrolizumab (Keytruda®), and nivolumab (Opdivo®). These and other immune checkpoint therapies represent  a new frontiers in conventional cancer treatments today. A few have scored some successes in recent years, particularly in some patients with metastatic melanoma or Hodgkin lymphoma. Checkpoint inhibitor Clinical trials involving patients with other types of cancer are pending.

Thus, it is still too soon to offer a definitive opinion about the usefulness of this therapy, notwithstand some short term success. What we know is that this therapy does not work for most cancer patients and that one of the toxic side effects is the creation of new auto-immune diseases where the killer T cells hunt down and attack healthy tissues. (See Blog).

Furthermore, the successful patients we have met using this conventional therapy have been seriously damaged for Life with their preceding chemo and radiation therapies. From what we saw, today’s conventional oncologists will either require the patient to first exhaust the chemo-radiation route first, or to put in place this checkpoint inhibitor immunotherapy in association with chemo or radiation. We have yet to have found a “virgin” patient that did only this therapy with success. On the other hand, with holistic immunotherapy, there are many cases we know of that have been successul with this approach right off the bat. (See Anecdotal Cases and Testimonials).

Pr Joubert (ACR director)

Reference and Precision Notes

(1). A checkpoint inhibitor blocks normal proteins on cancer cells, or the proteins on the T cells that respond to them. They are usually made from antibodies.

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