• Safety [ Designated as safety issue: Yes ]
  
• Frequency of T cells specific for LMP1-, LMP2-, and other Epstein-Barr virus antigens as well as T-cell specific for CMVpp65 based on ELISPOT or tetramer assays [ Designated as safety issue: No ]
  
• Immune function [ Designated as safety issue: No ]
  
• Antitumor activity [ Designated as safety issue: No ]
  

OBJECTIVES:

• To determine the safety of autologous or syngeneic LMP1- and LMP2-specific cytotoxic T lymphocytes (CTL) when given together with anti-CD45 monoclonal antibody in patients with relapsed Epstein-Barr virus-positive Hodgkin lymphoma, non-Hodgkin lymphoma, or EBV-associated T-/natural killer (NK)-lymphoproliferative disorders.
• To obtain information on the expansion, persistence and antitumor effects of autologous or syngeneic LMP1- and LMP-2 specific CTL given after lymphodepletion with anti-CD45 monoclonal antibody in these patients.

OUTLINE: This is a dose escalation study of LMP1- and LMP2-specific cytotoxic T lymphocytes (CTL).

Peripheral blood is collected from the patient or a donor and allogeneic or autologous dendritic cells (DC) are generated over 7 days using sargramostim (GM-CSF) and interleukin-4 (IL-4). DC are transduced with recombinant adenovirus encoding non-toxic LMP1 and LMP2 and matured with recombinant IL-4, GM-CSF, TNF-α, and prostaglandin (PGE-1) over 2 days to stimulate cytotoxic T lymphocytes (CTL). An Epstein-Barr virus (EBV)- transformed lymphoblastoid cell line is transduced with non-toxic LMP1 and LMP2 to produce CTL for infusion.

Patients receive anti-CD45 monoclonal antibody IV over 6-8 hours on days 1-4 and LMP1- and LMP2-specific CTL IV over 1-10 minutes on day 6, 7 or 8.

Blood samples are collected periodically during treatment for immune function studies, including total and differential lymphocyte count and immunophenotyping; immune function assays including analysis of frequency of T cells specific for test antigens such as cytomegalovirus or adenovirus as well as EBV using tetramer analysis, ELISPOT, or CTLp assays; cytotoxicity assays to look at specificity of response; and PCR for EBV DNA. Plasma-free anti-CD45 monoclonal antibody levels are also measured by flow cytometry 48-72 hours after final infusion of CD45 monoclonal antibody.

After completion of study treatment, patients are followed every 2 weeks for 8 weeks, at 3, 6, 9, and 12 months, and then periodically thereafter.