Immune Depletion to Enhance Immunotoxin Therapy

  • Resize font
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Name of the Trial

Pilot Study of Pentostatin plus Cyclophosphamide Immune Depletion to Decrease Immunogenicity of SS1P in Patients with Mesothelioma (NCI-11-C-0160). See the protocol summary.

Principal Investigator

Dr. Raffit Hassan, NCI Center for Cancer Research

Why This Trial Is Important  

Mesothelioma is a type of cancer that forms in the membranes that line the chest cavity and the abdominal cavity, as well as in the pericardium (heart sac). Biologically, this cancer is characterized, in part, by an overabundance of a protein called mesothelin. Few treatments are available for patients with advanced mesothelioma.

Researchers are investigating a treatment known as immunotoxin therapy in patients with mesothelioma and other types of cancer. In immunotoxin therapy, an antibody, or part of an antibody, is combined with a toxin that is capable of killing cancer cells. The antibody portion of the immunotoxin targets a protein that is overexpressed by the cancer cells, such as mesothelin, and delivers the toxin to the cells, while sparing cells that do not express the targeted protein.

Immunotoxin therapy has been used successfully in patients with some types of blood cancers. However, these patients typically have severely compromised immune systems, whereas patients with solid tumors, such as mesothelioma, often have fairly healthy immune systems. Because bacterial toxins are frequently used to make immunotoxins, patients with healthy immune systems will generally produce antibodies against these “foreign” proteins, thereby neutralizing, or inactivating, them. Therefore, for immunotoxin therapy to be effective against solid tumors, doctors must find ways to prevent the patient’s immune system from producing anti-immunotoxin antibodies.

NCI scientists have developed a pretreatment method, or “conditioning regimen,” that partially depletes a patient’s immune system, thus reducing the likelihood of an anti-immunotoxin immune response in patients receiving immunotoxin therapy. Animal studies have shown that pretreatment with the widely used anticancer drugs pentostatin and cyclophosphamide effectively prevents the formation of antibodies in mice treated with an immunotoxin called SS1(dsFv)-PE38 (also called SS1P), which targets mesothelin-producing cells. Mice given the conditioning regimen could be treated repeatedly with SS1P without forming antibodies against the immunotoxin, whereas mice not given the conditioning regimen developed antibodies after one administration of SS1P.

In this proof-of-concept pilot study, patients with advanced mesothelioma who have not benefited from previous chemotherapy will receive pentostatin and cyclophosphamide prior to and in conjunction with SS1P immunotoxin therapy. Doctors will use frequent blood tests and other studies to check for anti-SS1P antibodies. They will also assess the safety and tolerability of the combined therapy and evaluate tumor responses.

“Mesothelin is a protein normally present on the linings of the lungs and abdomen,” Dr. Hassan said. “But it is also highly expressed in many cancers, including mesothelioma, pancreatic, and ovarian cancers.

“SS1P is a targeted therapy to mesothelin. Previous clinical trials of SS1P showed hints of activity in patients with mesothelioma, but about 90 percent of patients developed immunogenic antibodies after only one cycle of treatment,” he continued. “We hope that a regimen of pentostatin and cyclophosphamide will prevent antibody formation and allow us to deliver multiple cycles of immunotoxin therapy.”

For More Information

See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

  • Posted: September 18, 2013

Most text on the National Cancer Institute website may be reproduced or reused freely. The National Cancer Institute should be credited as the source and a link to this page included, e.g., “Immune Depletion to Enhance Immunotoxin Therapy was originally published by the National Cancer Institute.”

Please note that blog posts that are written by individuals from outside the government may be owned by the writer, and graphics may be owned by their creator. In such cases, it is necessary to contact the writer, artists, or publisher to obtain permission for reuse.

We welcome your comments on this post. All comments must follow our comment policy.