Mesothelioma Cell Growth Affected by ADI-PEG 20 Plus Chemotherapy

Preliminary results from a Phase 1 study offer evidence that a combination of pegylated arginine deiminase plus pemetrexed and cisplatin chemotherapy can disrupt mesothelioma cell growth.

The results were announced in November by the Polaris Group, a biopharmaceutical company engaged in research and development of protein drugs to treat mesothelioma and other debilitating diseases.

The Polaris Group’s announcement followed a presentation of findings by the company’s research team at the Molecular Targets and Cancer Therapeutics Conference held in Boston earlier this month.

Deprives Mesothelioma of Vital Enzyme

Polaris Group refers to pegylated arginine deiminase in scientific shorthand as ADI-PEG 20. It causes cancer cells like mesothelioma to be deprived of needed arginine.

According to the company, arginine is one of the 20 amino acids a cancerous cell must have in order to be able to synthesize protein and survive. It turns out that mesothelioma cells cannot produce enough arginine on their own, so they have to steal large amounts of it from the circulatory system to survive.

The reason mesothelioma cells cannot make enough of their own arginine is that they are deficient in an enzyme called argininosuccinate synthetase – or ASS1. Polaris Group’s ADI-PEG 20 biotherapeutic is designed to reduce the amount of arginine that mesothelioma can steal by reducing its availability in the circulatory system.

Without that external supply of arginine, a mesothelioma cell will malfunction — hopefully enough so that it will die off.

The Phase 1 trial conducted by Polaris Group involved a total of just nine patients. Five of them were diagnosed with malignant pleural mesothelioma. The remainder had non-squamous non-small cell lung carcinoma, a close relative of mesothelioma.

One thing the patients all had in common was that their cancer cells were deficient in argininosuccinate synthetase.

The study entailed administering standard doses of pemetrexed plus cisplatin for the chemotherapy component and then adding increasingly larger doses of ADI-PEG 20.

“No dose limiting toxicity has been observed,” Polaris Group reported. “Seven patients had a partial response and two patients had stable disease as best response.”

The company’s research team noted that two of the five malignant pleural mesothelioma patients had the sarcomatoid form of the disease. The sarcomatoid type is normally the most difficult to treat and carries with it the poorest prognosis.

“One of the two sarcomatoid malignant pleural mesothelioma patients had a partial response while the other had stable disease,” the researchers said.

Hoping to Confirm Promising Results from ADI-PEG20

The researchers were elated to find that ADI-PEG 20 exhibited signs of strong clinical activity when paired with the twin chemotherapy drugs.

John Bomalaski, M.D., is the executive vice president of medical affairs for Polaris. He stated, “We are excited by the robust clinical activity seen in the dose escalating cohorts in both cancers. We look forward to confirming the promising results.”

Meanwhile, the company is also evaluating ADI-PEG 20 in a Phase 3 trial for hepatocellular carcinoma. Researchers at Polaris indicate they see promise for the biologic in other cancers, including leukemia, lymphoma, melanoma, breast cancer, ovarian cancer and pancreatic cancer.

In addition to the ADI-PEG 20 program, Polaris Group is researching and developing other biotherapeutic agents.

One involves a small molecule drug that utilizes “a rational structure-based approach” to the design of novel compounds. These compounds are capable of disrupting the functioning of cancer-related protein targets, the company indicates.