Autologous/Allogeneic TGFbeta-resistant LMP-specific CTL, Lymphoma (TGF-beta)

Description

Investigators will test a biopsy of the tumor to see if the tumor cells are EBV positive and to see if the subject is eligible for this study. Then they will take some blood from the donor, which is used to grow T cells. First they will grow a special type of cell called dendritic cells (or monocytes), which stimulates the T cells and add a specially produced human adenovirus that carries the LMP1 and LMP-2a genes into the dendritic cells(or monocytes). Addition of a gene to the cells is known as gene transfer. These dendritic cells (or monocytes) are then used to stimulate T cells. The stimulation trains the T cells to kill cells with LMP on their surface. Investigators will then make more LMP-specific CTLs by stimulating them with EBV infected cells (which we will make from the subject’s blood or the donor’s blood by infecting them with EBV in the laboratory). They also will put the adenovirus that carries the LMP1 and LMP2 genes into these EBV infected cells so that they increase the amount of LMP1 and LMP2, which these cells have.

These EBV infected cells are treated with radiation so they cannot grow. Once sufficient numbers of T cells are made, investigators test them to see if they kill cells with LMP on their surface. To make sure that these cells won’t attack the subjects tissues they test the cells against the skin cells or against T cells that they grow in the laboratory.

To make these CTL resistant to the effects of the TGFb released by the tumor we put in a new gene called a mutant TGFb receptor. Investigators used a mouse retrovirus that had been changed to stop it from causing infection to add the mutant TGFb receptor to the cells.

WHAT THE INFUSION WILL BE LIKE:

After the cells are made, they will be frozen. If the subject agrees to participate in this study, at the time they are scheduled to be treated, the cells will then be thawed and injected into the subject over 10 minutes.

Initially two doses of T cells will be given two weeks apart. If after the second infusion, there is a reduction in the size of the subject’s lymphoma (or no increase) on CT or MRI scans as assessed by a radiologist, the subject can receive up to six additional doses if it would be to their benefit, if they would like to receive more doses, and if there is enough product remaining to give them additional doses.

This is a dose escalation study as investigators don’t know what the highest dose of T cells with the new gene is safe. To find out, they will give the cells to 2 participants at one dose level. If that is safe they will raise the dose given to the next group of participants. The dose the subject will get will depend on how many participants get the agent before and how they react. The investigator will tell the subject this information.

All of the Treatments will be given by the Center for Cell and Gene Therapy at Texas Children’s Hospital or Houston Methodist Hospital.

FOLLOW-UP STUDIES We will follow the subject after the injections. Total time participation for this study will be 15 years.