June 20, 2024
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New Drug Candidate Could Boost Potential of Immunotherapy

One of the biggest breakthroughs in cancer treatment today is immunotherapy. Rather than flooding the body with toxic chemicals and radiation, this method recruits the patient’s own system to fight the cancer.

While the immune system’s job is to detect and destroy intruders, cancer cells have various ways to disable it. Immunotherapy, therefore, aims to help immune cells recover their natural function.

Although a powerful class of immunotherapy drugs, PD-1 inhibitors, was approved by the FDA in 2014, only 20-30 % of cancer patients respond well to them. Even among those who initially respond, often the therapy stops working once cancer cells learn how to evade PD-1 inhibitors.

“The reason seems to be that like cars in a traffic jam, the cancer cells find an alternative route to bypass the treatment, engage the immune cell [and shut it down],” explained Dr. Gavin Samuels, executive director of Jerusalem-based Nectin Therapeutics.

Cancer cells often use the nectin pathway to avoid the PD-1 pathway to disable immune cells.

Established in 2017 based on a collaboration between scientists at the Hebrew University of Jerusalem and the University of Rijeka, Croatia, Nectin Therapeutics’ drugs set up a roadblock in the nectin pathways.

Used alone or in conjunction with PD-1 inhibitors, this treatment could be a strong contender in the quest to boost the success of immunotherapy for cancer patients.

“There are probably many cells in our bodies that are constantly moving on a spectrum from normal cells to cancer cells, and an active immune system constantly surveys the situation,” explained Samuels, a physician.

“As soon as the immune system detects these abnormal cells, it attacks them.”

To protect themselves and take root as tumors, cancer cells develop anchors to reach specific receptors on the immune cell, fit into it like a key in a lock, switch it off and inactivate it.

By breaking that locking mechanism, immuno-oncology drugs reactivate the immune response and provide a safer treatment with fewer side effects than traditional chemo or radiation therapy.

“You have horrific side effects with chemotherapy because it’s essentially a poison that is more toxic to cancer cells — because they are rapidly dividing — than to normal cells,” Samuels explained. “We’ve developed a series of monoclonal antibodies and antibody-drug conjugates – an antibody with a toxin attached, sent directly to the cancer cell.”

Nectin Therapeutics’ drugs have been shown in preclinical studies to effectively restore the function of immune cells when used alone, and even more when combined with a PD-1 drug, he said.

The company’s lead candidate is expected to go into human clinical trials early next year. Other Nectin Therapeutics drugs could get to clinical trials about a year later, depending on FDA consideration, based on preclinical studies taking place in the US, Israel and Europe.

Nectin’s drugs use several different mechanisms of action to help restore the power of the immune system and shrink existing tumors.

By Abigail Klein Leichman/Israel21c

 

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