viernes, 22 de enero de 2016

Immunotherapy Trial HPV-Related Cancer - National Cancer Institute

Immunotherapy Trial HPV-Related Cancer - National Cancer Institute

National Cancer Institute

National Cancer Institute

Immunotherapy Trial for Patients with Metastatic HPV-Related Cancer

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Name of the Trial
T-Cell Receptor Gene Therapy Targeting HPV-16 E6 in Treating Patients with Metastatic, Recurrent, or Refractory HPV-Related Cancer (NCI-15-C-0005). See the protocol summary.
Dr. Christian Hinrichs
Credit: National Cancer Institute
Principal Investigator
Christian S. Hinrichs, M.D., NCI Center for Cancer Research
Why This Trial Is Important  
Human papillomavirus (HPV) infection is the most common sexually transmitted infection in the United States. In fact, most sexually active Americans will become infected with HPV at least once during their lifetime. In most cases, the immune system clears HPV infections within 6 months to 2 years, but longer lasting, or persistent, infections with certain HPV types known as oncogenic or “high-risk” types can lead to cancer.
Specifically, persistent infections with two high-risk HPV types, HPV-16 and HPV-18, are responsible for thousands of cancer cases and deaths each year in the United States and many times more worldwide. These HPV types account for most cervical, anal, genital, and oropharyngeal cancers. Of the two types, cancers caused by HPV-16 are more common than those caused by HPV-18.
In infected cells, high-risk HPV types produce viral proteins that promote the development of cancer. One of these proteins, known as E6, prolongs the survival of infected cells by causing the breakdown of a protein called p53, which normally suppresses tumor formation by triggering cell death (apoptosis). Indeed, in cell lines of HPV-16-related cancers, silencing the viral gene that encodes E6 causes the cells to die off.
Because HPV-16 E6 is only expressed in cancer cells and is required for those cells to survive, doctors believe it may be a good target for a type of immunotherapy treatmentcalled adoptive cell transfer (ACT).
In an ongoing clinical trial, researchers at NCI’s Center for Cancer Research extracted and isolated immune system cells from the tumors of patients with metastatic HPV-related cancers. These cells, so-called tumor-infiltrating lymphocytes, or TILs, were grown in the lab to greatly increase their numbers and then infused into the patients in hopes that they would unleash the patient’s immune system to attack the remaining cancer. Although only a fraction of patients have benefited so far from this treatment, early results demonstrate that ACT can be directed against HPV-induced cancers and produce lasting responses.
In the current trial, the researchers are trying a different type of ACT in patients with advanced HPV-16-related cancers. By genetically modifying immune cells to express cell-surface receptors that recognize E6, doctors hope that the therapy will produce better and more consistent responses among patients.
“One of the limitations of our initial approach is that we don’t always get TILs with good reactivity to the viral oncoproteins, and, if that happens, there’s really nothing we can do to make those cells reactive,” said Dr. Christian Hinrichs, the trial’s principal investigator. “Additionally, we have to surgically remove a metastatic tumor and then isolate and grow the TILs, all of which takes time.
“So to try to produce a more broadly applicable therapy, we developed this new approach, which is called T-cell receptor gene therapy. With this method we take T lymphocytes from the peripheral blood and genetically modify them to express a T-cell receptor that can recognize the E6 oncoprotein on tumor cells,” he explained.
In this trial, patients with metastatic or treatment refractory cancer caused by HPV-16 infection will undergo a lymphocyte-depleting chemotherapy regimen followed by a single infusion of T-cell receptor modified T cells and intravenous infusion of aldesleukin for up to 5 days. Treatment and recovery, along with follow-up appointments, will take place at theNIH Clinical Center in Bethesda, Maryland. Doctors want to see if the cancer responds to the treatment and how long the responses last, as well as determine the safety of the therapy. They will also conduct tests to see if any biological differences can be identified between patients who do and do not respond.
For More Information
See the lists of eligibility criteria and trial contact information, or call the Surgery Branch Recruitment Center at 866-820-4505. The toll-free call is confidential.

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