Safety Study of Injections of Autologous/Allogeneic TGFbeta-resistant LMP2A-specific Cytotoxic T-lymphocytes (CTL) (TGF-beta)

Patients have a type of lymph gland cancer called Hodgkin Disease, non-Hodgkin Lymphoma or lymphoepithelioma (these 3 diseases will be referred to as "Lymphoma"). The lymphoma has come back or has not gone away after treatment (including the best treatment we know for these cancers).

We are asking patients to volunteer to be in a research study using special immune system cells called TGFb-resistant LMP-specific cytotoxic T lymphocytes (DNR-CTL), a new experimental therapy. Patients may have already thought a lot about being in this study. They may even have already made a decision about whether to be in the study. Even if this is true for the patient, it is important that we give the patient this information and talk about it before we start them in the study.

Some patients with Lymphoma show signs of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of the Lymphoma. EBV is found in the cancer cells of up to half the patients with Lymphoma, suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed by releasing a substance called Transforming Growth Factor-beta (TGFb). We want to see if special white blood cells (called T cells) that have been given a gene that we hope will let them survive against TGFb and that have been trained to kill EBV infected cells and can also survive in the blood and kill the tumor.

We have used this sort of therapy with specially trained T cells to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post transplant lymphoma. In this type of cancer we were able to successfully prevent and treat post transplant lymphoma. However when we used a similar approach in Hodgkins disease some patients had a partial response to this therapy, but no patients had a complete response.

In a follow-up study we tried to find out if we could improve this treatment by growing T cells that recognize two of the proteins expressed on Lymphoma cells called LMP-1 and LMP2a. These special T cells were called LMP-specific cytotoxic T-lymphocytes (CTLs). Although some patients had tumor responses, CTL therapy alone did not cure patients who had a lot of disease. We think that a reason for this is that the tumor cells are releasing TGFb, which is a substance that inhibits the growth and function of CTLs. For this reason we want to find out if we can make the CTL resistant to TGFb by putting in a new gene called TGFb resistance gene. We hope but do not know that this will improve this treatment for relapsed lymphoma. These TGFb-resistant LMP-specific cytotoxic T lymphocytes are an investigational product not approved by the Food and Drug Administration.