Administration of LMP1- and LMP2-Specific Cytotoxic T-Lymphocytes to Patients With EBV-Positive Nasopharyngeal Carcinoma
Patients have an EBV-positive cancer. We had gotten permission to take blood from patients
in the past, which was used to grow T cells in the laboratory. We first grew a special type
of cell called dendritic cells to stimulate the T cells. We then put a specially produced
human virus (adenovirus) that carries the LMP1 and LMP2 gene into the dendritic cells. These
dendritic cells were then treated with radiation so they could not grow. They were then used
to stimulate T cells. This stimulation trained the T cells to kill cells with LMP1 and LMP2
on their surface. We then grew these LMP1- and LMP2-specific CTLs by more stimulation with
EBV infected cells (which we made from blood by infecting them with EBV in the laboratory
and treated them with radiation so they would not grow). We also put the adenovirus that
carries the LMP1 and LMP2 genes into these EBV infected cells so that we increase the amount
of LMP1 and LMP2 that these cells have. Once we made sufficient numbers of T cells we tested
them to make sure they kill cells with LMP1 and LMP2 on their surface. These cells are now
ready to give to the patients if they agree to participate in this study.
If the patient agrees to this treatment they will get treated with two doses of LMP1-and
LMP2-specific CTLs, each dose given 2 weeks apart. If the patient is a female of
child-bearing potential, we will give them a pregnancy test within one week prior to the
infusion. If the patient is pregnant, they will not be able to participate in the study. The
study doctor will be notified.
The CTLs will be thawed and injected through a central line, if they have one, or through a
vein in their arm over 1 to 10 minutes. They may receive a dose of Tylenol and Benadryl
beforehand. We will then monitor the patient in clinic for 1 to 4 hours after the injection.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas
Children's Hospital or the Methodist Hospital. We will follow the patient in the clinic
after the CTL injection and also follow results of their disease evaluations with the
To learn more about the way the T cells are working and how long they last in the body, an
extra 10-60 mls (2-12 teaspoonfuls) of blood will be taken. We will use this blood to look
at the immune response in the blood to the cancer.
To learn if the injected T cells have anti-tumor activity, we will measure the size of the
patient's tumor before the T-cell infusion and 8 weeks afterwards with routine imaging
studies such as CT (computer tomogram), MRI (magnetic resonance imaging), or PET (Positron
Emission Tomography). If the patient has stable disease or there is a reduction in the size
of the tumor on imaging studies after the T-cell infusion, the patient can receive up to six
additional doses of the T cells at 6 to 12 weeks intervals if they wish.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
adverse events are being measured/assessed for the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in patients with EBV-positive nasopharyngeal carcinoma (NPC).
Stephen Gottschalk, MD
Baylor College of Medicine
United States: Food and Drug Administration
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|