NCI Research Unlocks Potential of Immunotoxins
An inability to unlock the vast potential of the SS1P immunotoxin and use it effectively for patients with mesothelioma has frustrated researchers for many years.
Those days of frustration may have ended.
Medical oncologist Raffit Hassan, M.D., believes his team of researchers at the National Cancer Institute (NCI) has found the right accompanying drug combination to allow SS1P to work more effectively, providing a significant breakthrough against mesothelioma.
Hassan will detail his findings Oct. 29 at the 15th World Conference on Lung Cancer in Sydney, Australia. Those findings first appeared last week in Science Translational Medicine.
“We believe this is pretty significant. We’re excited about the findings,” Hassan told Asbestos.com from his office at the NCI before leaving for Australia. “Everyone was pleasantly surprised. What we found could benefit other cancers, too.”
Suppressing Immune System Is Key
Although a strong immune system often is the best defense against serious illnesses, effectively suppressing the immune system was the key to SS1P working effectively and reducing tumor size in late-stage mesothelioma patients who were part of a small clinical trial.
The immune suppressors used were pentostatin and cyclophosphamide, in conjunction with the SS1P immunotoxin.
“These were patients who were very sick, with huge amounts of disease,” Hassan said. “We never expected this type of positive response. It was a very pleasant surprise.”
SS1P is classified as a recombinant immunotoxin, a drug that links a bacterial toxin to an antibody fragment that can selectively target a particular molecule, allowing it to kill cancer cells without killing healthy ones. SS1P targets cells with mesothelin, which is elevated particularly in mesothelioma, ovarian and pancreatic cancers.
Prior to Hassan’s recent finding, the problem has been that mesothelioma patients often develop antibodies to the same immunotoxins and reduce the effectiveness of SS1P. The cyclophosphamide and pentostatin working together showed an ability to prevent the buildup of those antibodies, which allowed SS1P to work much better.
The trial involved 10 advanced-stage mesothelioma patients who enrolled between December 2011 and October 2012. Three of them had significant tumor shrinkage. One woman experienced a 74 percent tumor shrinkage that was maintained through the last follow-up at 15 months.
Two more responded positively to chemotherapy after the SS1P therapy was discontinued. The key, according the study results, was that the antibody development, which had neutralized the SS1P in the past, had been slowed. In six of the 10, there was a noted elevation in concentrations of SS1P within the patients, suggesting the drop in the production of neutralizing antibodies.
Need for Larger Trial Now
“The next step would be to confirm the findings through a larger trial,” said Hassan, who has been working with SS1P for more than 10 years and developing therapies for mesothelioma for 15 years.
The safety of SS1P was established earlier at the NCI through two Phase I clinical trials that included 58 patients: 36 with mesothelioma, 19 with ovarian cancer and three with pancreatic cancer.
Although the SS1P was tolerated well, none of the original 36 mesothelioma patients had any significant tumor response. And 90 percent of those developed neutralizing antibodies after only one cycle of treatment.
The results prompted the latest pilot study involving pentostatin and cyclophosphamide, which was tested earlier using mice in the laboratory.
“Some people told us, these drugs would not work,” Hassan said. “But we persisted. The findings could go well beyond mesothelioma.”