Genetically Engineered Immunotherapy for Advanced Cancer || NCI Cancer Bulletin for August 7, 2012 - National Cancer Institute

NCI Cancer Bulletin for August 7, 2012 - National Cancer Institute
Genetically Engineered Immunotherapy for Advanced Cancer

Genetically Engineered Immunotherapy for Advanced Cancer

Name of the Trial
Phase I/II Study of Metastatic Cancer Using Lymphodepleting Conditioning Followed by Infusion of Anti-Mesothelin Gene Engineered Lymphocytes (NCI-12-C-0111). See the protocol summary.

Dr. Steven Rosenberg

Principal Investigator
Dr. Steven Rosenberg, NCI Center for Cancer Research
Why This Trial Is Important

NCI researchers have been at the forefront of efforts to develop a type of immunotherapy called adoptive cell transfer (ACT). This kind of therapy involves collecting immune system cells from a patient, growing them in the laboratory to many times their original number, and then infusing the cells into the patient to fight his or her cancer. To ensure the survival and optimal functioning of the infused cells, the number of immune cells in the patient's body must be substantially reduced before the cell infusion. This type of preparatory treatment is called lymphodepletion or conditioning.

In one type of ACT, doctors obtain T lymphocytes from the patient's blood and then genetically engineer the cells to recognize and bind to a protein, or antigen, found on the surface of the patient's cancer cells, which will help activate the immune system against these cells. The genetically modified lymphocytes are then multiplied in the laboratory and infused into the patient, where, if the treatment works, they will kill cells that express the targeted antigen.

One potential antigen target is mesothelin, a protein found on normal cells (mesothelial cells) that make up the membranes that line the lungs, heart, and abdominal organs, as well as some other parts of the body. The amounts of this protein are often increased in malignant tumors, including almost all mesotheliomas and pancreatic adenocarcinomas and some types of lung, ovarian, esophageal, and head and neck cancers, making it an attractive target for immunotherapy.

Led by Dr. Steven Rosenberg, researchers in NCI's Center for Cancer Research are exploring the potential of genetically engineering peripheral blood T lymphocytes to recognize and attack cancer cells that express mesothelin.

In this phase I/II clinical trial, researchers will collect T lymphocytes from the blood of patients with metastatic or unresectable cancer that expresses mesothelin and has not responded to previous systemic therapy and genetically engineer these T lymphocytes to recognize mesothelin. The genetically modified cells will then be grown in culture to expand the number of cells, which will be infused into the patients after they have undergone lymphodepleting conditioning. The patients will also receive low-dose aldesleukin, which is a cytokine that will help keep the infused cells alive.

In the phase I part of this trial, groups of patients, called cohorts, will be treated with differing doses of infused lymphocytes to establish a maximum tolerated dose. The phase II part of the trial will involve treating patients with mesothelioma or other mesothelin-expressing cancers at the maximum tolerated dose. All patients will undergo treatment at the NIH Clinical Center in Bethesda, MD, where doctors will assess the safety and effectiveness of this 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.

Further reading: "Complex Immune-Based Cancer Treatment Shows Signs of Progress"

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/featured.