Checkpoint Inhibitors… Cancer’s Penicillin Moment (Beginning Of The End)

by ProfKeith

Penicillin changed the world. Virtually overnight hundreds of diseases that formerly killed millions of people were rendered impotent. Life expectancy shot up by decades. The prospect of a long and happy life became a reality for the majority of those in the Western word.

Today, the main killers are self-inflicted: heart disease, diabetes and cancer… yes, cancer. The Big C has been known for a long time to be a disease of Western lifestyle factors.

It’s best not to get it (my advice!) but if you do, the road to recovery can be long and hard. You’d be forgiven for thinking that a lot of people die of the treatment, not the cancer. You’d be pretty correct.

But now things are changing… FAST.

I’ve been saying for years that if only medical science would follow nature’s path, we could solve this pretty quickly. It’s the immune system that saves cancer victims, not stupid chemo and radiation. These blunderbuss treatments harm the immune system and so are counter-productive on the whole (the lucky people are those who have formidable detoxing capabilities).

checkpoint-inhibitors-blunderbusA blunderbuss: sprays wide and hits nothing in particular, except by pure luck!

Now a really significant breakthrough has emerged, much as I predicted in my   newsletters: harnessing the amazing powers of natural immunity.

Scientists are now working along the lines of outsmarting a cancer, instead of blasting it to kingdom come. Even the frightening malignant melanoma is succumbing to crafty signals.

There is new generation of anticancer drugs – called checkpoint inhibitors – that are having such a profound impact that some scientists are calling it a turning point in cancer treatment, a “penicillin moment”!

“Melanoma and lung cancer used to be death sentences, but they’re not any more,” says Gordon Freeman at the Dana-Farber Cancer Institute in Boston. “It’s a revolution, and it’s only the start.”

Now a rapidly expanding group of patients, despite starting out with a really bleak prognosis such as melanoma or lung cancer, are surviving years, instead of the usual months. Jimmy Carter was the lucky recipient of this new treatment, which has cleared a potentially lethal melanoma from his brain. May have gone into what appears to be permanent remission.

What’s Going On with Checkpoint Inhibitors?

The story of these treatments began in the 1960s when Tasuku Honjo a Japanese trainee doctor, learned of the death of a close classmate from gastric cancer. “My dream became to cure cancer,” he says.

The dream began to materialize 30 years on, in 1992 when, as an immunologist at the University of Kyoto, he was studying how and why important immune cells we call T-cells sometimes self-destruct. He discovered a protein produced on the surface of some T-cells and suspected it was involved in this process. So he called it “Programmed cell death-1, or PD-1.

To find out what PD-1 does, Honjo disabled the gene that makes the protein in mice. He found that they developed autoimmune disease, including mild arthritis, heart degeneration and joint disease.

This tells us that PD-1 puts a brake on the immune system. That’s the last thing you want when fighting cancer! Honjo started to wonder whether the immune system could be unleashed against cancer by blocking PD-1 with a drug.

This fits with our known holistic model of cancer defense: that the immune system is ultimately what wipes out the disease. The immune system recognizes cells that are “foreign” and blasts them out of existence, using nature’s wonderful very specific weapons (blunderbuss… NOT!)

See, one of the reasons that cancer is so good at thriving and spreading in the body is its ability to dampen down the immune system. For this reason, most conventional treatments have used brute force, zapping tumor cells with drugs or radiation.

The problem is, such treatments are unspecific, damaging healthy cells alongside the tumors. Plus they are unable to keep up with cancer as it evolves in response to their onslaught (developing resistance).

Better would be to find a way to loosen the chokehold that cancer cells have over the immune system, letting it do the job it is supposed to do. Attempts so far have included a range of vaccines and immune-stimulators and the results have been encouraging, showing this is the way to do. But nothing has worked really consistently well.

Till now!

About six years ago, came sensational results from a trial of a drug called ipilimumab, or “ipi” for short, which had unprecedented effects against melanoma, the most lethal type of skin cancer. Some 45 per cent of people were still alive a year after the trial ended, and 24 per cent were alive after a further year – around four times better than standard chemotherapies.

That’s a Wow!

More strikingly, there was a subset of people who seemed to be almost completely rid of their cancer. “Around 20 percent of the patients survived longer than three years,” says Jedd Wolchok of the Memorial Sloan-Kettering Cancer Center in New York City, one of the main clinicians involved in testing the drug. “Some are still alive 10 or 11 years later.”

Once people have reached three years survival, they seem to go on indefinitely without the cancer coming back, according to Wolchok.

Unfortunately, ipi turned out to be very toxic. Side effects included lung inflammation and hepatitis. Some patients died.

What seemed to be happening in most cases was that the whole immune system went into overdrive, slaughtering healthy cells as well as cancerous cells in its blitzkrieg. What was needed was a much more targeted approach.

That’s where Honjo’s idea comes in. Following the reasoning deeper and deeper, it was found that PD-1 attracted a molecule now known as PD-L1 (programmed death ligand-1). Crucially, they also discovered that cancerous cells often produce PD-L1. “The first ones we found were on ovarian and breast cancer cells,” says Freeman. “Then, we found it on lots of other cancer cells, and realized that PD-L1 seemed to be the trick cancers used to turn on the immune brake.

That was the ‘aha’ moment.”

What Freeman, Honjo and their teams had discovered is that PD-L1 on the surface of cancer cells formed what they called “a truce-like handshake” with PD-1. This calls off the immune attack, allowing the cancer to proliferate unchallenged.

So could blocking PD-1 stymie cancer? To test the idea, Honjo tried growing human tumors in mice engineered to lack PD-1. Sure enough, he found that the tumors wouldn’t grow.

checkpoint-inhibitors-machine-gun

“The immune system machine-guns the tumor rather than taking one potshot“

That’s better!

The next step was to make antibodies against PD-1, to see if they would protect against cancer by “releasing the brake”. They did, although not as well as knocking the gene out completely. But it was enough to show that it was possible to give the immune system the desired boost.

At first Big Pharma didn’t want to know. “I tried to convince the pharmaceutical industry, but with enormous difficulty,” Honjo says.

That changed with the realization that the side effects of ipi often outweigh the benefits, meaning their profits were lowered. Finally, the pharmaceutical industry turned its attention to the PD-1 system, and PD-1 inhibitor drugs, which are now setting the oncology world alight.

The two forging ahead are nivolumab, or “nivo”, and pembrolizumab, or “pembro”, the drug used to treat Jimmy Carter (who dreams up these clunky names?)*.

One reason the drugs are proving so successful is that remobilizing the immune system allows it to continuously evolve to keep the tumor in check, limiting the ability of the cancer to escape detection and destruction even if it develops hundreds of mutations. The immune system doesn’t see one target on the tumor, it sees 10, or 50 maybe, so it machine-guns the tumor, rather than taking a single pot-shot. It’s a lot harder to evade a machine gun.

There is a significant downside: these drugs only work for some of the people who receive them. “In lung cancer, two or three out of 10 have very significant responses, or their disease is stable for a long time,” says Julie Brahmer of Johns Hopkins University of Medicine in Baltimore, Maryland, and co-leader of some of the PD-1 inhibitor trials. “But the majority of lung cancer patients are not responding, and that’s where the work is now.”

Please hurry up!

Meanwhile, you can get an insight into all the scores of other workable methods of defeating cancer from my comprehensive masterwork, Cancer Research Secrets.

*Yes, I know: they are spat out in ribbons by some computer and they choose the ones that are pronounceable!

[SOURCE: New Scientist, 5 Mar 2016, Volume 229, No 3063, p. 34]

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