Immune Depletion to Enhance Immunotoxin Therapy
Name of a Trial
Pilot Study of Pentostatin and Cyclophosphamide Immune Depletion to Decrease Immunogenicity of SS1P in Patients with Mesothelioma (NCI-11-C-0160). See a custom summary.
Dr. Raffit Hassan, NCI Center for Cancer Research
Why This Trial Is Important
Mesothelioma is a form of cancer that forms in a membranes that line a chest form and a abdominal cavity, as good as in a pericardium (heart sac). Biologically, this cancer is characterized, in part, by an overabundance of a protein called mesothelin. Few treatments are accessible for patients with modernized mesothelioma.
Researchers are questioning a diagnosis famous as immunotoxin therapy in patients with mesothelioma and other forms of cancer. In immunotoxin therapy, an antibody, or partial of an antibody, is total with a venom that is able of murdering cancer cells. The antibody apportionment of a immunotoxin targets a protein that is overexpressed by a cancer cells, such as mesothelin, and delivers a venom to a cells, while provident cells that do not demonstrate a targeted protein.
Immunotoxin therapy has been used successfully in patients with some forms of blood cancers. However, these patients typically have exceedingly compromised defence systems, since patients with plain tumors, such as mesothelioma, mostly have sincerely healthy defence systems. Because bacterial toxins are frequently used to make immunotoxins, patients with healthy defence systems will generally furnish antibodies opposite these “foreign” proteins, thereby neutralizing, or inactivating, them. Therefore, for immunotoxin therapy to be effective opposite plain tumors, doctors contingency find ways to forestall a patient’s defence complement from producing anti-immunotoxin antibodies.
NCI scientists have grown a pretreatment method, or “conditioning regimen,” that partially depletes a patient’s defence system, so shortening a odds of an anti-immunotoxin defence response in patients receiving immunotoxin therapy. Animal studies have shown that pretreatment with a widely used anticancer drugs pentostatin and cyclophosphamide effectively prevents a arrangement of antibodies in mice treated with an immunotoxin called SS1(dsFv)-PE38 (also called SS1P), that targets mesothelin-producing cells. Mice given a conditioning fast could be treated regularly with SS1P though combining antibodies opposite a immunotoxin, since mice not given a conditioning fast grown antibodies after one administration of SS1P.
In this proof-of-concept commander study, patients with modernized mesothelioma who have not benefited from before chemotherapy will accept pentostatin and cyclophosphamide before to and in and with SS1P immunotoxin therapy. Doctors will use visit blood tests and other studies to check for anti-SS1P antibodies. They will also consider a reserve and tolerability of a total therapy and weigh growth responses.
“Mesothelin is a protein routinely benefaction on a linings of a lungs and abdomen,” Dr. Hassan said. “But it is also rarely voiced 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, though about 90 percent of patients grown immunogenic antibodies after usually one cycle of treatment,” he continued. “We wish that a fast of pentostatin and cyclophosphamide will forestall antibody arrangement and concede us to broach mixed cycles of immunotoxin therapy.”
For More Information
See a lists of eligibility criteria and hearing hit information or call a NCI Clinical Trials Referral Office during 1-888-NCI-1937. The call is fee giveaway and confidential.