A new cancer treatment tricks the immune system into attacking

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Immunotherapy holds perhaps the greatest promise for fighting cancer in the 21st century. Rather than bombarding the body with toxic chemicals, as in chemotherapy, immunotherapy uses the immune system to neutralize malignant tumors.

The only problem: it only works in about 20% of patients with solid tumors.

The reason is simple, but still a frustrating hurdle for cancer researchers: tumors are not an infection from outside but an internal malfunction of the body’s own cells, which begin to replicate uncontrollably.

“Cancer looks like us. It’s hard for the immune system to identify,” says Dr. Asher Nathan, CEO of NeoTX, a Rehovot-based startup that is developing a new way to eliminate tumors by coating them with bacteria.

“Unlike cancer, our bodies are finely tuned to attack bacteria,” says Nathan. “Bacteria are a billion years old. Our immune system has had a long time to figure out how to effectively neutralize bacterial infections. That’s why you don’t wake up in the morning with a cold and think, ‘I’m going to die.’

Cancer, of course, is a very different story. Compared to bacteria, “cancerous tumors are like the new kid on the block,” Nathan notes.

NeoTX isn’t Nathan’s first foray into medical technology; after immigrating to Israel 40 years ago from Chicago, he founded IntelliGene and EvoRX, two biotech companies formed around technologies he invented.

For NeoTX, Nathan identified and licensed a drug developed by Swedish company Active Biotech called naptumomab estafenatox (NAP).

NAP is made up of two proteins: a genetically modified “superantigen” and an antibody that attaches to a tumor via a molecule called 5T4 that is found mainly on tumors.

A superantigen is a bacterial derivative that elicits a strong antibacterial immune response. NeoTX calls its technology “Tumor-Targeted Superantigen” or TTS.

Once the NAP 5T4 antibody attaches to a tumor, the superantigen “reprograms” the immune system to mount an antibacterial response against the bacteria as well as the tumor.

“The concept behind this drug is to coat the tumor with a bacterial molecule so that the immune system enters ‘Defcon 1’ and attacks the tumor as if it were bacteria,” says Nathan.

The secret weapon

Once the immune system knows what to look for, it sends the body’s secret weapon: killer T cells.

T cells identify tumors coated with bacteria, then begin to create an army of cells ready to attack any superantigens they find. Nathan recommends the video below to see how T cells work; they “grope like a blind robot” and after touching a superantigen, punch a hole in the cell…then insert a molecule that explodes the cell.

It’s a nice balance. When fighting a bacterial infection, “the body can go crazy,” Nathan notes. “You may have a high fever which depletes the immune system. This is how the bacteria keep fighting. We genetically modified our superantigen to be safer. It doesn’t generate such a strong response, but it still creates a very strong immune reaction. »

Targeting bacteria is smart for another reason: Part of how tumors manage to evade the body’s defenses is by releasing chemicals that weaken the immune response.

“Anything we do near the tumor becomes problematic,” says Nathan. But with NAP, “tumor-killing T cells are created far from the site of the immunocompromised tumor.” Only then do they begin their journey to find and destroy the tumors.

Additionally, when the immune system encounters a tumor-bound superantigen, it alters the suppressive microenvironment around the tumor so that the body’s natural defenses are better able to kill it.

“It creates a natural, holistic, deep immune response,” says Nathan.

Reboots the immune system

Dr. Asher Nathan, CEO of NeoTX. Photo courtesy of NeoTX

But the best may be yet to come.

“When we tested this drug in animals, we found that even when you try to put cancers back into, say, a mouse that’s been cured by technology, it doesn’t stick,” says Nathan.

“None of the mice that were ‘reintroduced’ got the cancer again. The drug ‘wakes up’ the immune system – at least in the mice – and we don’t need the drug anymore.

Nathan compares it to the restart function of a computer. “The drug reboots the immune system so it can do what it natively needs to do – suppress the suppressive environment and kill as many tumor cells as possible. Then the T cells can aim for more targets.

NeoTX’s bacterial coating approach is currently undergoing a Phase I trial in Israel and, based on encouraging results, has begun a Phase 2 trial in the United States with 30 patients.

A patient has non-small cell lung cancer that has metastasized to the liver. “It’s a death sentence, usually within four months,” says Nathan. The patient received the drug from NeoTX over ten years ago (before it was licensed by Active Biotech). “She lived 11 years and died of something else, not her cancer.”

NAP works particularly well with checkpoint inhibitors, another type of cancer treatment that aims to reduce cancer-created “checkpoints” that essentially trick T cells into thinking the tumor is a tumor. friend.

“It’s like a secret handshake in a college fraternity,” jokes Nathan.

If the handshake was inhibited, so to speak, the T-cells would see the tumor for what it is – it really isn’t a friend – and could attack. Combining NAP with a checkpoint inhibitor “allows our drug to kill more tumor cells,” says Nathan.

AstraZeneca Collaboration

Pharmaceutical giant AstraZeneca is collaborating with NeoTX on its own checkpoint inhibitor technology. The hope is that patients who do not respond normally will have more success in the fight against their cancer.

The development and commercialization of any new drug can take up to 15 years and several million dollars. NeoTX has raised around $80 million so far. Nathan is optimistic that if NAP passes phase 2 and 3 trials, it could hit the market as early as 2027.

Although the technology has so far been tested on solid cancerous tumors of the lung, esophagus and urethra, patients with blood cancers such as lymphoma and leukemia could also benefit – especially those who are candidates for CAR-T, a promising treatment that involves removing T-cells from a patient, engineering them for maximum killing capacity in a lab, and then injecting them back.

CAR-T, a form of immunotherapy, tends to work well for blood cancers but poorly for solid tumors. This is another objective of NeoTX: to provide a pharmaceutical supplement that will allow CAR-T to be effective outside the field of blood cancers.

Immunotherapy has become a crowded field. “If you look at all the companies trying to elicit an immune system response, there are probably 1,000. But for the specific mechanism we’re trying, it’s zero,” Nathan notes.

“One of our investors told us, ‘You’re either geniuses or you’re crazy.’ I said, ‘What makes you think it’s one or the other?’

NeoTX is no shortage of geniuses. Roger Kornberg, winner of the 2006 Nobel Prize in Chemistry, is the company’s chief scientist (as well as a longtime collaborator of Nathan in his previous projects).

Michael Levitt and Arieh Warshel, who shared a 2013 Nobel Prize in Chemistry, are advisers. Dr. Marcel Rozencweig, a medical oncologist and 18-year veteran of pharmaceutical company Bristol Myers Squibb, where he was head of global oncology, is the chairman of NeoTX.

Recently, the Head of Global Clinical Oncology at Bayer Pharmaceuticals, Dr. Scott Fields, joined NeoTX as Chief Medical Officer.

“It’s extremely rare for someone as high-ranking as Scott Fields to leave the pharmaceutical industry to work in such a small company,” Nathan told ISRAEL21c. “It’s even rarer for him to come to a company based in Israel.”

Cancer, unfortunately, is not going away anytime soon. “The average person develops about five cancerous or precancerous cells a day,” Nathan notes.

“Our bodies are very efficient at killing, so most people don’t get a new cancer every day. Our drug could level the playing field so the body can do what it’s supposed to do.

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