A large cancer cell surrounded by NK (Natural killer) cells – the cancer-killing molecules work only where they are supposed to.In the war against cancer, Israeli scientists Dr. Angel Porgador and Dr. Ofer Mandelboim are on the front lines of weapons development.

Porgador, of Ben-Gurion University of the Negev and Mandelboim of the Hebrew University in Jerusalem are generating cancer-killing molecules that will recognize cancerous cells and target them aggressively, while not affecting normal cells.

These cutting-edge warheads – called Natural Killer cells are among the first cells of the immune response that arrive at the site of infection or inflammation, and their major function is to kill their target cells. The researchers believe that harnessing them will bypass the problematic side-effect of current chemotherapy drugs, which, though effective in killing cancer cells, often also destroy normal tissues.

Today, most anti-cancer therapies are not specific in the systems they attack, and as a result, can cause severe side effects on normal tissues such as immune system cells, skin, hair and gut epidermal cells.

Porgador describes the molecules he and Mandelboim are generating as “micro-missiles.”

“The cancer-killing molecules work only where they are supposed to,” he told ISRAEL21c. “They are ‘natural’, derived from the receptors expressed by killer cells that recognize and eliminate tumor and virus-infected cells.”

The tumor-targeting approach is based on molecules that can identify their target by attaching themselves to special receptors on the cancer cells, thus identifying and eliminating only the harmful cancer cells while keeping the normal healthy body cells unharmed.

The therapeutic drug that the researchers hope will emerge from their research will recognize tumor cells and bind to the diseased cell and destroy it. The drug will also, by itself or combined with other compounds, improve the efficacy and safety of chemotherapy agents.

These new anti-cancer molecules are currently in the pre-clinical stage with extensive animal research and if all goes well, clinical tests will begin in the near future with humans. The researchers claim that the new tumor-targeting strategy has the potential to affect many kinds of cancers and to revolutionize the way the disease is treated. Foremost among them is the possibility of avoiding many of the devastating side effects that chemotherapy can cause.

“The paradox of so many anti-cancer drugs is that their efficiency as killers of cancer cells makes them toxic to normal tissues as well,” said Porgador.

While many researchers around the world are trying to figure out how to attack cancer without side effects, Porgador explains that the approach of the Israeli team is unique.

“We did not invent the field of tumor targeted therapy. There are hundreds of startup companies in the world working to target tumors and avoid the side effects using a biotoxin and chemotoxin,” he said. “Our advantage in regard in comparison to the hundreds of companies that are targeting tumors is that we are using the natural material of the body; we are basically isolating the natural targeting mechanism.”

In order to advancing the potential applications of their research, Porgador and. Mandelboim have launched a company called NatSpears, which is under the umbrella of the RAD Biomed incubator.

Utilizing the duo’s proprietary expertise in the NK recognition mechanism, the company’s aim is to create novel, smart targeted therapies for a wide range of tumors, with high efficacy and a clean side-effect profile. The company is currently focused on accelerating the development of two lead molecules for prostate and melanoma cancer.

The CEO of NatSpears is Dr. Eyal Fima, who holds a post-doctoral position at the Faculty of Health Sciences in Ben-Gurion University of the Negev and has extensive cancer therapy research and management experience.

Thus far, NatSpears’ animal experiments have shown that when their prototypes are injected into mice into which human prostate and melanoma tumors are introduced, the tumors have been reduced in size, and some have been rejected.

NatSpears represents the latest collaboration for Mandelboim and Porgador, who have been friends since the early days of their studies. They met while doing graduate work together at the Weizmann Institute of Science, and continued their collaboration during their post-graduate stints in the United States – Porgador at Duke University and the U.S. government’s National Institute of Health, and Mandelboim at Harvard University.