This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HYPOTHESIS We propose to develop and test an innovative approach to adoptive immunotherapy for EBV +ve Hodgkin disease (HD) and Non-Hodgkin's Lymphoma (NHL). We have previously shown adoptive transfer of donor derived EBV specific cytotoxic T lymphocytes is effective treatment and therapy for EBV associated lymphoproliferative diseases after bone marrow transplantation. Having shown that the EBV-positive cells in post-transplant lymphoproliferation (LPD) are susceptible to immunotherapy, we hypothesize that the malignant cells in Hodgkin disease and EBV associated NHL arising in immunocompetent patients, which express a more restricted repertoire of EBV encoded antigens, are also suitable targets for immunotherapy. We have already evaluated the use of EBV specific CTL, which recognize all 9 latent EBV antigens in such patients, and shown evidence of persistence, augmentation of anti-EBV immunity and evidence of antitumor response in some patients. In this current protocol, we will test the hypothesis that CTL lines with defined specificity against the LMP2a antigen expressed by these tumor cells (LMP2 specific CTLs) are safe, increase patient immune responses to EBV encoded antigens and have anti-tumor effects.
SPECIFIC AIMS : 1) To determine the safety of autologous LMP2A-specific cytotoxic T-lymphocytes (CTL) in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector. 2) To determine the survival and the immune function of LMP2A-specific cytotoxic T-lymphocyte lines. 3) To assess the anti-viral and anti-tumor effects of LMP2A-specific CTLs. 4) To obtain preliminary information on the safety and response to an extended dosage regimen.
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