The subject has a type of cancer or lymph gland disease associated with a virus called Epstein Barr Virus (EBV), which has come back, is at risk of coming back, or has not gone away after standard treatments. This research study uses special immune system cells called LMP, BARF-1 and EBNA1- specific cytotoxic T lymphocytes (MABEL CTLs).

Some patients with Lymphoma (such as Hodgkin (HD) or non-Hodgkin Lymphoma (NHL)), T/NK-lymphoproliferative disease, or CAEBV, or solid tumors such as nasopharyngeal carcinoma (NPC), smooth muscle tumors, and leiomyosarcomas show signs of a virus called EBV before or at the time of their diagnosis. EBV causes mononucleosis or glandular fever ("mono" or the "kissing disease"). EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells (in CAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. EBV is also found in the majority of NPC and smooth muscle tumors, and some leiomyosarcomas. Investigators want to see if special white blood cells (MABEL CTLs) that have been trained to kill EBV infected cells can survive in patients blood and affect the tumor.

In previous studies, EBV CTLs were generated from the blood of the patient, which was often difficult if the patient had recently received chemotherapy. Also, it took up to 1-2 months to make the cells, which is not practical when a patient needs more urgent treatment. To address these issues, the MABEL CTLs were made in the lab in a simpler, faster, and safer way. The MABEL CTLs will still see LMP proteins but also two other EBV proteins called EBNA-1 and BARF. To ensure these cells are available for use in patients in urgent clinical need, investigators have generated MABEL CTLs from the blood of healthy donors and created a bank of these cells, which are frozen until ready for use. Investigators have previously successfully used frozen T cells from healthy donors to treat EBV lymphoma and virus infections and we now have improved our production method to make it faster.

In this study, investigators want to find out if they can use banked MABEL CTLs to treat HD, NHL, T/NK-lymphoproliferative disease, CAEBV, NPC, smooth muscle tumors or leiomyosarcoma. Investigators will search the bank to find a MABEL CTL line that is a partial match with the subject.

MABEL CTLs are investigational and not approved by the Food and Drug Administration.

A healthy donor has given blood to make LMP/BARF1/EBNA-1 MABEL CTLs in the lab. Investigators made the cells by first growing a special type of cells called activated T cells to stimulate the T cells. Investigators then added specially produced mixtures of proteins that include the LMP, EBNA1 and BARF proteins. These were used to stimulate T cells. As the T cells grew, investigators added some of the healthy donor cells expressing these proteins to stimulate them. Investigators also added a cell called K562 that has had new genes put inside it so it expresses proteins that stimulate the immune system to encourage the T cells to grow. K562 cells are cancer cells that have been treated with radiation so they cannot grow. This stimulation trained the MABEL CTLs to kill cells with EBV proteins on their surface. These cells were grown and frozen.

For the subject's treatment, the MABEL CTLs will be thawed and infused into the subject over 1-10 minutes. Initially, two doses of MABEL CTLs will be given two weeks apart. Subjects may be eligible to receive additional doses of the MABEL CTLs up to 6 times.

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

Medical tests before treatment:

Before being treated, the subject will receive a series of standard medical tests:

Physical exam; Blood tests to measure blood cells, kidney and liver function; Tumor measurements by routine imaging studies: Computer Tomogram (CT), Magnetic Resonance Imaging (MRI), or Positron Emission Tomography (PET/CT); Pregnancy test for females who are able to have children.

Several studies suggest that the infused T cells need room to be able to proliferate and accomplish their functions and that this may not happen if there are too many other T cells in circulation. Because of that, if the patient's level of circulating T cells is relatively high, s/he may require treatment with cyclophosphamide (Cytoxan) and fludarabine before s/he receives MABEL CTLs.

Medical tests during and after treatment:

Blood tests to measure blood cells, kidney and liver function; Imaging study 8 weeks after the 1st CTL infusion. If the subject receives additional doses they will also have an imaging study at 1 to 3 months after their final dose.

Subjects will either be seen in the clinic or will be contacted by research staff yearly for 5 years.

Inclusion Criteria:

SCREENING

1. Any patient regardless of age or sex, with diagnosis of either:

   • EBV positive Hodgkin's lymphoma
   • EBV Positive non-Hodgkin's Lymphoma (regardless of histologic subtype)
   • EBV (associated)-T/NK-lymphoproliferative disease
   • Severe Chronic Active EBV (CAEBV) -- CAEBV is defined as patients with high EBV viral load in plasma or PBMC (>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
   • Other EBV positive malignancies (e.g. nasopharyngeal carcinoma, smooth muscle tumors, etc.)

   AND

   • in first or subsequent relapse (Group A)
   • with active disease persisting despite therapy (Group B)
   • with active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group C)

2. EBV positive tumor

3. Weighs at least 12kg

4. Informed consent (and assent as applicable) obtained from patient/guardian.

TREATMENT

1. Any patient regardless of age or sex, with diagnosis of either:

   • EBV positive Hodgkin's lymphoma
   • EBV Positive non-Hodgkin's Lymphoma (regardless of histologic subtype)
   • EBV (associated)-T/NK-lymphoproliferative disease
   • Severe Chronic Active EBV (CAEBV) -- CAEBV is defined as patients with high EBV viral load in plasma or PBMC (>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
   • Other EBV positive malignancies (e.g. nasopharyngeal carcinoma, smooth muscle tumors, etc.)

   AND

   • in first or subsequent relapse (Group A)
   • with active disease persist despite therapy (Group B)
   • with active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group C)

2. EBV positive tumor

3. Patients with life expectancy greater than or equal to 6 weeks

4. Patients with bilirubin less than or equal to 3x upper limit of normal

5. AST less than or equal to 5x upper limit of normal

6. Hemoglobin greater than or equal to 7.0 (may be a transfused value)

7. Patients with a creatinine less than or equal to 2x upper limit of normal for age

8. Pulse oximetry of > 90% on room air

9. Patients should have been off other investigational therapy for 30 days prior to infusion.

10. Patients with a Karnofsky/Lansky score of more than or equal to 50.

11. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

12. Informed consent (and assent as applicable) obtained from patient/guardian.

Exclusion Criteria:

TREATMENT

1. Pregnant or lactating
2. Severe intercurrent infection
3. Current use of systemic corticosteroids more than 0.5 mg/kg/day
4. Patients receiving ATG, Campath, or other immunosuppressive T cell monoclonal antibodies within 30 days.